COLD SPRING HARBOR SYMPOSIA

ON QUANTITATIVE BIOLOGY

VOLUME XXXII

COLD SPRING HARBOR SYMPOSIA

ON QUANTITATIVE BIOLOG Y

Founded in 1933

by REGINALD G. HARRIS

Director of the Biological Laboratory

1924 to 1936

The Symposia were organized and managed by Dr. Harris until his death. Their continued use-

fulness is a tribute to the soundness of his vision

The Symposium Volumes are published by the Cold Spring Harbor

Laboratory of Quantitative Biology Cold Spring Harbor, L.I., New York

COLD SPRING HARBOR SYMPOSIA

ON QUANTITATIVE BIOLOGY

VOLUME XXXII

ANTIBODIES

COLD SPRING HARBOR LABORATORY OF QUANTITATIVE BIOLOGY COLD SPRING HARBOR, L.I., NEW YORK

1967

COPYRIGHT �9 1968 BY

THE COLD SPRING HARBOR

LABORATORY OF QUANTITATIVE BIOLOGY

Library of Congress

Catalog Number: 34-8174

All rights reserved. This book may not be reproduced in whole or in part except by reviewers for the public press without written permission from the publisher.

Printed in the U.S.A.

The Symposium Volumes are published by the Cold Spring Harbor Laboratory of Quantitative Biology. Cold Spring Harbor, New York, and may be purchased directly or through booksellers.

Price of Volume 32--$20.00 (inc. postage). Price subject to change without notice.

FOREWORD

Having held our previous symposium on the Genetic Code, it seemed natural to turn directly from that to the subject of Antibodies. The code epitomizes living systems at their most inflexible; not only is the same method of protein synthesis used throughout the plant and animal kingdoms, but it seems that even the same language is spoken by all living things. By way of contrast, the formation of specific antibodies denotes extreme versatility. This versatility appears, at first sight, to be in direct conflict with the central dogma of molecular biology which maintains that the primary structure of proteins is encoded in nucleic acids, not improvized. Thus the recent deciphering of the genetic code provided a most appropriate background for a symposium on antibodies.

Apart from current events in the microbiological world, this would still have been a suitable year for discussing the mechanism of antibody formation. Sequence analysis of normal and pathological immunoglobulins was providing an ever more detailed picture of the end-product of immunogenesis. And the prospect seemed bright that the mechanism of antibody formation, once the subject for so many unsubstantiated theories, was about to develop its own dogmas.

I am happy to acknowledge the help of our advisors in preparing the program. In particular, I wish to thank Drs. Gerald Edelman, Stephen Fazekas de St. Groth, Niels Jerne, and Gus Nossal, who bore the brunt of the consultation. The task of assembling this volume has been carried out by our editor, assisted by Harriet D. Hershey and Elspeth Cairns.

The meeting was held from the 1st to the 7th of June, 1967, and was attended by about 300 people, including 40 from outside the United States. As in the past, the program was supported by the National Institutes of Health, United States Public Health Service; the National Science Foundation; the United States Atomic Energy Commission; and the United States Air Force Office of Scientific Research (under grant AF-AFOSR-1299-67).

John Cairns, Editor: Leonora Friseh Director.

LIST OF PREVIOUS VOLUMES

Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume Volume

Volume

Volume Volume Volume

Volume Volume Volume Volume Volume Volume Volume Volume

I (1933) Surface Phenomena, 239 pp. II (1934) Aspects of Growth, 284 pp. III (1935) Photochemical Reactions, 359 pp. IV (1936) Excitation Phenomena, 376 pp. V (1937) Internal Secretions, 433 pp. VI (1938) Protein Chemistry, 395 pp. VII (1939) Biological Oxidations, 463 pp. VIII (1940) Permeability and the Nature of Cell Membranes, 285 pp. IX (1941) Genes and Chromosomes. Structure and Organization, 315 pp. X (1942) The Relation of Hormones to Development, 167 pp. XI (1946) Heredity and Variation in Microorganisms, 314 pp. XII (1947) Nucleic Acids and Nucleoproteins, 279 pp. XIII (1948) Biological Applications of Tracer Elements, 222 pp. XIV (1949) Amino Acids and Proteins, 217 pp. XV (1950) Origin and Evolution of Man, 425 pp. XVI (1951) Genes and Mutations, 521 pp. XVII (1952) The Neuron, 323 pp. XVIII (1953) Viruses, 301 pp. XIX (1954) The Mammalian Fetus. Physiological Aspects of Development,

225 pp. XX (1955) Population Genetics: The Nature and Causes of Genetic Variability

in Population, 346 pp. XXI (1956) Genetic Mechanisms: Structure and Function, 392 pp. XXII (1957) Population Studies: Animal Ecology and Demography, 437 pp. XXIII (1958) Exchange of Genetic Material: Mechanism and Consequences,

450 pp. XXIV (1959) Genetics and Twentieth Century Darwinism, 321 pp. XXV (1960) Biological Clocks, 524 pp. XXVI (1961) Cellular Regulatory Mechanisms, 408 pp. XXVII (1962) Basic Mechanisms in Animal Virus Biology, 535 pp. XXVIII (1963) Synthesis and Structure of Macromolecules, 610 pp. XXIX (1964) Human Genetics, 492 pp. XXX (1965) Sensory Receptors, 649 pp. XXXI (1966) The Genetic Code, 762 pp.

SOME SYMPOSIUM PARTICIPANTS

Fi~-qt Row" J. E. Till, L. Siminovitch - - C. Baglionl, E. S. Lennox - - W. E. Paul, A. M. Pappeaheimer, A. H. Coons. Second Row" G. M. Edelman, P. Vassalli - - M. E. Koshland, M. Fishman, G. J. V. Nossal - - - O. Smithies, R. J. Poljak. Third Row" J. Sterzl, W. J. Dreyer - - C. Milstein, R. N. Perham, L. Hood, E. Appclla - - F. Haurowitz, F. H. C. Crick. Fourth Row: S. J. Singer, W. O. Weigle, S. ])ray - - A. E. Bussard, M. Simonsen, Mrs. Bussard - - A. B. Stavitsky, M. G.

Mage, E. Weiler, H. N. Eisen, R. G. Mage.

SOME S Y M P O S I U M P A R T I C I P A N T S

Fi rs t Row: N. K. J e r n e - - C. Davern , M. N a u g h t o n , S. F a z e k a s de St. Gro th - - M. Burner , B. Benaceraff . Second Row: P. G. H. Gell, B. Pe rn i s - - M. Weiger t , B. Maeh, F. A. Sher, J . L. F a h e y - - R. W. D u t t o n , G. L. Ada. Third Row: A. Suran, R. A. Reisfeld, J : Sjoquis t , S. D r a y - - D. W. Ta lmage , B. Benaceraff , H. N. E i sen - - G. J . V. Nossa l

Mrs. M. Cohn, M. Cohn. Fou r th ROW: L. Wofsy, G. M. E d e l m a n - - D. H. Campbel l , B. Cinader , B. V. Siegel, O. Smi th ies - - L. A. Herzenberg ,

S. Dubisk i , B. Cinader. (Pho tog raphs by E. Gall and A. Bernhe imer , Jr . )

List of Those Attending the Symposium

ACTON, RONALD T., Dept. of Microbiology, University of Alabama Medical Center, Bir- mingham, Alabama 35233

ADA, G. L., The Walter & Eliza Hall Institute of Medical Research, Dept. of Biochemistry & Biophysics, Post Office, Royal Melbourne Hospital, Victoria, Australia

ADLER, FRAN]~ L., Public Health Research Institute of New York City, Foot of East 16 Street, New York, N.Y.

ALADJEM, FREDERICK, University of Southern California School of Medicine, Dept. of Microbiology, Los Angeles, California

AMBROSE, CHARLES T., Harvard Medical School, Dept. of Bacteriology & Immunology, 25 Shattuck Street, Boston, Mass. 02115

AMKRAUT, ALFRED A., Oregon Regional Primate Research Center, Dept. of Immunology, 505 N.W. 185 Ave., Beaverton, Oregon 97005

APPELLA, ETTORE, National Cancer Institute, National Institutes of Health, Laboratory of Biology, Bethesda, Maryland 20014

ASKONAS, BRIGITTE A., National Institute for Medical Research, Mill Hill, Dept. of Immu- nology, London, N.W. 7, England

BAGLIONI, CORRADO, Int. Laboratory of Genetics and Biophysics, Via Marconi 10, Naples, Italy

BEAR, PHYLLIS, Genetics Research Unit, Carnegie Inst. of Wash., Cold Spring Harbor, N.Y.

BECKER, MILTON J., Dept. of Biology 16-730, Massachusetts Institute of Technology, Cam- bridge, Mass.

BENACERRAF, BARUJ, New York University School of Medicine, Dept. of Pathology, 550 First Avenue, New York, N.Y. 10016

BENGELSDORF, IRVING S., Los Angeles Times, Science Editor, Los Angeles, California 90053

B~RN~IMEH, ALAN JR., Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York 11724

BERNSTEIN, BARBARA LISOWSKA-, New York University Medical Center, Dept. of Pathology, New York, N.Y. 10016

BRANDT, CHARLES W., Medical College of Virginia, Richmond, Virginia 23219

BURGI, ELIZABETH, Genetics Research Unit, Car- negie Inst. of Wash., Cold Spring Harbor, New York

BURNET, SIR M.ACFARLANE, School of Micro- biology, University of Melbourne, Parksville, N.2, Victoria, Australia

BURR, BENJAMIN, Dept. of Bacteriology, Uni- versity of California Berkeley, California 94720

BUSSARD, ALAIN E., Institut Pasteur, Dept. Cellular Immunology 28 Rue du Docteur Roux, Paris 15, France

ix

BVXBAVM, JOEL, New York University School of Medicine, Dept. of Medicine, 550 First Ave., New York, N.Y.

CAIRNS, JOHN, Cold Spring Harbor Laboratory of Quantitative Biology, Cold Spring Harbor, New York 11724

CAHNMANN, HANS J., NIAMD, National Institutes of Health, Bcthesda, Maryland 20014

CAMPBELL, DAN H., California Institute of Technology, Dept. of Chemistry, 1201 East California Blvd., Pasadena, Calif. 91109

CAPRA, J. DONALD, Lab of Biochemistry, National Inst. of Dental Research, NIH, Bethesda, Maryland 20014

CARR, RONALD I., The Rockefeller University, New York, N.Y. 10021

CATHOU, RENATA E., Massachusetts General Hospital, Cardiac Unit, Boston, Mass.

CEBRA, JOHN J., Johns Hopkins University, Dept. of Biology, Baltimore, Maryland. Present address: Dept. of Immunology, St. Mary's Hospital, London, England

CHASE, MERRILL W., The Rockefeller University, Dept. of Immunology, 66 Street and York Avenue, New York, N.Y. 10021

CI4AVIN, STEPHEN I., New York University School of Medicine, Dept. of Medicine, 550 First Avenue, New York, N.Y. 10016

CINADER, BERNHARD, University of Toronto, Dept. of Medical Biophysics, 500 Sherbourne Street, Toronto 5, Ontario, Canada

CIOLI, DONATe, Int. Laboratory of Genetics and Biophysics, Casella Postale 3061, Naples, Italy

CLEM, L. WILLIAM, University of Florida, Dept. of Microbiology, Gainesville, Florida

COHEN, EDWARD P., Rutgers Medical School, Dept. of Microbiology, New Brunswick, New Jersey

CORN, MELVIN, The Salk Institute for Biological Studies, P.O. Box 1809, San Diego, California

COLLOMS, MICHAEL D., University of California, Dept. of Bacteriology and Immunology, Berkeley, California 94720

CONVERSE, CAROLYN, The Massachusetts General Hospital, Boston, Mass. 02114

CooNs, ALBERT H., Harvard Medical School, Dept. of Bacteriology & Immunology, 25 Shattuck Street, Boston, Mass. 02115

COOPER, DR. HERBERT L., National Institutes of Health, Dept. of Cell Biology, National Inst. of Dental Research, Bethesda, Md.

CRICK, FRANCIS, MRC Lab of Molecular Biology, Hills Road, Cambridge, England

DAVERN, CEDRIC, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724

DAvis, BRIAN, McGill University Chemistry Dept., Montreal, Canada

x LIST OF THOSE ATTENDING THE SYMPOSIUM

DARNELL, JOHN H., University of Pennsylvania Medical School, Dept. of Biochemistry Philadelphia, Pennsylvania

DINTZIS, HOWARD M., The Johns Hopkins Univer- sity School of Medicine, Dept. of Biophysics, Baltimore, Maryland 21205

DORNER, MARIANNE, Columbia University College of Physicians and Surgeons, New York, N.Y.

DORIA, GINO, Euratom, Gruppo Cnen-Euratom di Immunogenetica, Centro Studi Nucleari Della Casaccia, S.P. Anguillarese Roma, Italia

DRAu SHELDON, University of Illinois at the Medical Center, Dept. of Microbiology, P.O. Box 6998, Chicago, Ill. 60680

DREYER, WILLIAM J. Division of Biology, California Institute of Technology, Pasadena, California

DUEISKI, S., The Toronto Western Hospital, Dept. of Immunology, 399 Bathurst Street, Toronto 2B, Canada

DUTTON, RICHARD W., Scripps Clinic and Research Foundation, Dept. of Exp. Pathology, 476 Prospect Street, La Jolla, Calif. 92037

EDELMAN, GERALD M., The Rockefeller University, Dept. of Biochemistry, New York, N.Y. 10021

EDWARDS, JOSHUA L., Indiana University Med. Sciences Program, 103 Myers Hall, Blooming- ton, Indiana

EHRENSTEIN, GUNTER, VON The Johns Hopkins University School of Medicine, Dept. of Biophysics, Baltimore, Maryland 21205

EIN, DANIEL, National Cancer Institute, Immunol- ogy Branch, Bethesda, Maryland

EISEN, HERMAN N., Washington University, Dept. of Microbiology 600 S. Kings Highway, St. Louis, Missouri 63110

FAHEY, J. L., National Cancer Institute, Immu- nology Branch, Bethesda, Maryland

FAZEKAS DE ST. GROTH, S., Commonwealth Scientific and Industrial Research Organiza- tion, Division of Animal Genetics, North Ryde, N.S.W., Australia

FELDBUSH, THOMAS L., Merck & Company, Inc., Merck Institute, Rahway, New Jersey

FINEGOLD, IRA, Room 4B18, Building 10, Immu- nology Branch, National Institutes of Health, Bethesda, Maryland 20014

FISHMAN, MARVIN, Public Health Research Institute of New York City, Inc. Dept. of Immunology, Foot of East 16 Street, New York, N.Y. 10009

FLEISCHMAN, JULIAN B., Washington University School of Medicine, Preventive Medicine & Microbiology Dept., St. Louis, Mo. 6311

FOUGEREAU, MICHEL, I.N.R.A., Laboratoire d'Immunologie, 78-Thiverval, Grignon, France

FOWLER, ELIZABETH, Dept. Biological Chemistry, Cardiac Research Lab, Massachusetts General Hospital, Boston, Mass. 02114

FRANKLIN, EDWARD C., NYU School of Medicine, Dept. of Medicine, 550 First Avenue, New York, N.Y. 10016

FREEDMAN, MURRAY H., Roswell Park Memorial Institute, Biochemistry Research, 666 Elm Street, Buffalo, New York 14203

FRIEDMAN, HERMAN, Albert Einstein Medical Center, Dept. of Microbiology, York and Tabor Roads, Philadelphia, Penna. 1914

FRISCH, LEONORA, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.

FUKUI, GEORCE M., Wallace Laboratories, Dept. of Microbiology, Half Acre Road, Cranbury, New Jersey 08512

GALIZZI, ALESSANDRO, Johns Hopkins Medical School, Dept. of Biophysics, Baltimore, Md.

GALL, W. EINAR, The Rockefeller University, Dept. of Biochemistry, New York, N.Y. 10021

GALLY, JOSEPH A., The Rockefeller University, Dept. of Biochemistry, New York, N.Y. 10021

GAREN, SUZANNE, Yale University Medical School, New Haven, Conn.

GELL, P. G. H., University of Birmingham Medical School, Dept. of Exp. Pathology, Edgbaston, Birmingham 15, England

GENCO, ROBERT S., Dept. Medical Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania

GLENN, WILLIAM G., USAF School of Aerospace Medicine, Dept. of Microbiology, Brooks Air Force Base, San Antonio, Texas 78235

GEWURZ, HENRY, National Institutes of Health, Bethesda, Maryland 20014

GOLDSTEIN, DANIEL J., Dept. of Biophysics, Johns Hopkins University School of Medicine, Baltimore, Md. 20205

GOODMAN, JOEL W., University of California, School of Medicine Dept. of Microbiology, San Francisco, Calif. 94122

GOTTLIEB, PAUL D., The Rockefeller University, Dept. of Biochemistry, New York N.Y. 10021

GowANs, J. L., Sir William Dunn School of Pathology, Dept. Cellular Immunology, Oxford University, Oxford, England

GRAY, GARY D., The Upjohn Company, Dept. of Biochemistry, Henrietta Street, Kalamazoo, Michigan

GREEN, IRA, New York University School of Medicine, Dept. of Pathology, 550 First Avenue, New York, N.Y. 10016

GREENBERO, L. J., NYU School of Medicine, Irvington House Institute and Dept. Pathol- ogy, 560 First Ave., New York, N.Y.

GROSSBERO, ALLAN L., Roswell Park Memorial Institute, Dept. of Biochemistry Research, 666 Elm Street, Buffalo, N.Y. 14203

GREY, HOWARD M., Scripps Clinic & Research

LIST OF THOSE ATTENDING THE SYMPOSIUM xi

Foundation, Dept. of Exp. Pathology, 476 Prospect Street, La Jolla, California 92037

GUNSALUS, I. C., Dept. of Chemistry & Chem. Eng., Biochemistry Division, University of Illinois, Urbana, Illinois 61801

HABEEB, A.F.S.A., St. Jude Childrens Research Hospital, Dept. of Biochemistry, 332 N. Lauderdale, Memphis, Tennessee 38101

HABER, EDGAR, Massachusetts General Hospital, Cardiac Unit, Fruit Street, Boston, Mass. 02114

HAMERS, R., University of Brussels, Laboratory of Animal Physiology, 57 Rue des Chevaus, Rhode Sct Genese, Belgium

HALAC, ELIAS, New York University, 560 First Avenue, New York, N.Y.

HARRIMAN, PHILIP, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y. 11724

HARSHMAN, SIDNEY, Dept. of Microbiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37203

HARTMAN, KLAuS-ULRICH, Max Planck Institut for Virus Research, Spemannstr. 35, Tubingen, Germany

HAUROWITZ, FELIX, Dept. of Chemistry, Indiana University, Bloomington, Indiana 47401

HAUTLY, VERA (Mrs. B. W. Papermaster) Univer- sity of California, Berkeley. Present address: Roswell Park Memorial Institute for Cancer Research, Buffalo, New York.

HATHAWAY, PETER, Cornell Medical Center, Div. of Human Genetics, New York, N.Y.

HAVAS, H. FRANCIS, Temple University Health Science Center, Dept. of Microbiology, Phila., Penna. 19140

HENLEY, WALTER, Dept. of Immunochemistry, Rockefeller University, New York, N.Y.

HERSHEY, A. D., Genetics Research Unit, Carnegie Inst. of Wash., Cold Spring Harbor, N.Y.

HERSHEY, HARRIET, Cold Spring Harbor Labora- tory, Cold Spring Harbor, New York

HERZENBERG, L. A., Dept. of Genetics, School of Medicine, Stanford University, Palo Alto, California 94304

HICHENS, MARTIN, Merck Institute, Dept. of Biochemistry, Rahway, New Jersey 07065

HOOD, L., Biology Division, California Institute of Technology Pasadena. Present address National Cancer Institute, NIH, Bethesda, Maryland

HUMPHREY, RICHARD L., Johns Hopkins Univer- sity, Dept. of Biophysics, & Medicine, School of Medicine, 725 N. Wolfe Street Baltimore, Maryland 21205

HYMAN, ROBERT, University of California, Dept. of Bacteriology & Immunology, Berkeley, Cali- fornia 94720.

INGRAHAM, LAURA, Genetics Research Unit,

Carnegie Inst. of Wash. Cold Spring Harbor, N.Y.

IRIMAJIRI, SHOICHIRO, New York University Medical Center, Dept. of Medicine, 550 First Avenue, New York, N.Y.

ITIKAWA, HIRAKU, McCollum-Pratt Institute, The Johns Hopkins University, Baltimore, Md.

JARO~KOVA', L. 1050 George Street, New Bruns- wick, New Jersey

JERNE, NIELS K., Paul Ehrtich Institute, Paul Ehrlich Strasse 42-44, 6000 Frankfurt/M.S.- 10, Germany

JERRY, L. MARTIN, Rockefeller University, c/o Dr. Kunkel's Laboratory, New York, N.Y.

KANTOR, FRED S., Yale University, Dept. of Internal Medicine, 333 Cedar Street, New Haven, Conn.

KARAM, J. D., Cold Spring Harbor Laboratory, Cold Spring Harbor, New York

KARUSH, FRED, University of Pennsylvania School of Medicine, Dept. of Microbiology, Phila- delphia, Penna. 19104

KEMPER, JOST, Public Health Research Inst. of the City of New York, Inc. Foot of E. 16th St. New York, N.Y.

KENNEDY, JAMES C., Salk Institute for Biological Medicine, Lab of Dr. E. S. Lennox, P.O. Box 1809, San Diego, Calif., 92112

KERN, MZLTON, National Institutes of Health, NIAMD, Lab of Biochemistry & Metabolism, Bldg. 10, Rm. 9B-11, Bethesda, Md. 20014

KING, DONALD WEST, University of Colorado Medical Center, Dept. of Pathology, 4200 E. Ninth Ave., Denver, Colorado 80220

KNIGHT, K. L., University of Illinois Medical Center, Dept. of Microbiology, Chicago, Illinois 60680

KNOPF, PAUL M., Salk Institute, P.O. Box 1809, San Diego, Calif. 92112

KSLSCH, ECKEHART, The Salk Institute for Biological Studies, P.O. Box 1809, San Diego, California 92112

KONIGSBERG, WILLIAM, 120 Highland Park Road, North Haven, Conn. 06473

KOSHLAND, MARIAN E., University of Califor- nia, Virus Laboratory, Berkeley, California

KUMAR, SHUSHIL, Public Health Research Inst. of the City of New York, Inc. Foot of E. 16th St. New York, N.Y.

LAMELIN, J. P., Dept. of Pathology, New York University, 550 First Avenue, New York, N.Y.

LAMM, MICHAEL, New York University School of Medicine, Dept. of Pathology, 550 First Avenue, New York, N.Y. 10016

LA VIA, MARIANO F., University of Colorado Medical Center, Dept. of Pathology, 4200 East 9th Avenue, Denver, Colorado 80220

xii LIST OF THOSE ATTENDING THE SYMPOSIUM

LAWRENCE, H. S., Dept. of Medicine, New York University medical Center, Inf. Dis. & Immunol. Div., 550 First Ave., New York, N.Y.

LAVRIN, DAVID, University of Illinois, College of Medicine, Dept. of Microbiology, P.O. Box 6998, Urbana, Illinois

LECCE, JAMES G., Animal Science Dept., Box 5658 State College Sta., North Carolina State University, Raleigh, N.C. 27607

LENNOX, EDWIN S., The Salk Institute for Bio- logical Studies, P.O. Box 1809, San Diego, California 92112

LEVY, DAVID A., Johns Hopkins University School of Hygiene & Public Health, 615 N. Wolfe Street, Baltimore, Md. 20215

LEWIS, HERMAN, National Science Foundation, Cellular Biology Sect., 1800 G Street, Washing- ton, D.C. 20550

LICHTER, EDWARD A., University of Illinois Medical Center, Preventive Medicine and Com- munity Health Dept., 1853 W. Polk St., Chicago, Illinois 60612

LIEBERMAN, ROSE, National Institutes of Health, NIAID, Building 10, Room 11N321, Bethcsda, l~aryland 20014

LINDA_HL, TOMAS, Princeton University, Chemistry Dept., Princeton New Jersey 08540

LITT, MORTIMER, Channing Laboratory, 818 Harrison Ave., Boston, Mass. 02118

LIu, CHI-TAN, Public Health Research Institute of the City of New York, Foot of East 16 Street, New York, N.Y.

LonG, CAROL, Dept. of Microbiology, University of Pennsylvania, School of Medicine, Phila- delphia, Penna. 19104

MAC DOWELL, E. CARLETOI~-, Cold Spring Harbor Laboratory, Cold Spring Harbor, N.Y.

McCLINTOCK, BARBARA, Genetics Research Unit, Carnegie Inst. of Wash., Cold Spring Harbor, New York 11724

McCLURE, WILLIAM 0., Dept. of Biochemistry, Rockefeller University New York, N.Y. 10021

McCULLOCH, E. A., Ontario Cancer Institute and University of Toronto, Dept. of Medical Biophysics and Medicine, 500 Sherbourne Street, Toronto 5, Ont., Canada

McDEvITT, HUGH 0., Stanford University Med. Center, Dept. of Medicine, Div. of Immunology, Palo Alto, 94309, California

MCILWAINE, ISABELLE, Johns Hopkins University, Dept. of Biology 34 St. & Charles St., Balti- more, Maryland 21218

MCINTIRE, K. ROBERT, National Cancer Institute, Laboratory of Biology, National Institutes of Health, Bethesda, Md. 20014

MCNAMARA, PETER, Rutgers State University, Dept. of Microbiology, New Brunswick, N.J.

MACH, BERNARD, Institute of Molecular Biology, University of Geneva, 24 Quai de l'Ecole de Medecine, Geneva, Switzerland

MAGS, MICHAEL G., Lab of Biochemistry, N.C.I., Bethesda, Maryland 20014

MAGE, ROSE G., Lab of Immunology, NIAID, 9000 Rockville Pike, Bethesda, Maryland

1VIXKELX, 0., State Serum Institute, Helsinki, Finland

MAKOVER, SHRAGA, Genetics Research Unit, Carnegie Inst. of Wash., Cold Spring Harbor, N.Y. 11724

MALLEY, ARTHUR, Oregon Regional Primate Research Center, Dept. of Immunology, 505 N.W. 185 Avenue, Beaverton, Oregon 97005

MANUEL, YVES, Institut Pasteur, Lyons, France MARCHALONIS, JOHN J., Dept. of Biochemistry,

Rockefeller University, New York, N.Y. MARGOLIN, PAUL, Public Health Research Inst.

of the City of New York, Inc. Foot of E. 16th St., New York, N.Y.

MARSHALL, W. H., Inf. Dis. & Immunol. Div., NYU Medical Center, 550 First Avenue, New York, N.Y. 10016

MEISS, HARRIET KAUFMAN, Gruppo CNEN- Euratom di Immunogenetica Comitato Nazi- onale Per L'Energia Nucleare, Centro d Studi Nucleari Della Casaccia, S. P. Anguill arese km 1-300, Roma, Italia

MELCHERS, FRITZ, Salk Institute for Biological Studies, P.O. Box 1809, San Diego, California

MERRYMAN, CARMEN, New York Blood Center, 310 East 67 Street, N.Y.

MERRYMAN, Philip, 444 Central Park West, New York, N.Y.

METCALF, R. DONALD, Roswell Park Memorial Institute, 666 Elm Street Buffalo, New York 14203

METZGER, HENRY, National Institutes of Health, NIAMD, Bethesda, Maryland 20014

MILLER, RICHARD G., The Ontario Cancer Institute, Dept. of Physics, 500 Sherbourne Street, Toronto 5, Canada

MILSTEIN, C., MRC Lab of Molecular Biology, Hills Road, Hammersmith Hospital, Cam- bridge, England

MISHELL, ROBERT I., Scripps Clinic and Research Foundation, Dept. of Exp. Pathology, 476 Prospect Street, La Jolla, Calif. 9203

MITCHISON, N. A., National Institute for Medical Research, Dept. of Experimental Biology, Mill Hill, London, N.W. 7, England

MONTGOMERY, PAUL C., Richards Research Build- ing, University of Pennsylvania, Philadelphia, Penna.

MOROZ, C., Dept. of Medicine, New York University, 550 First Avenue, New York, N.Y.

LIST OF THOSE ATTENDING THE SYMPOSIUM xiii

MULLINAX, FRANKLIN, Dept. of Medicine, Medical College of Virginia, 1200 E. Broad Street, Richmond, Virginia 23219

MUNRO, ALAN J., University of Cambridge, Dept. of Biochemistry, Tennis Court Road, Cam- bridge, Englan.d

MUSHINSKI, J. FREDERIO, National Institutes of Health, Carcinogenesis Section, Bldg. 8, Room 202, National Cancer Institute, Beth- esda, Maryland 20014

NATVIG, JACO~ B., The Rockefeller University, New York, N.Y.

NAUGHTON, M., Dept. of Biophysics, Johns Hopkins Medical School, 725 N. Wolfe Street, Baltimore, Maryland 21205

NISONOFF, A~LFRED, University of Illinois College of Medicine, Dept. of Microbiology, Chicago, Illinois

NOSSAL, G. J. V., Hall Institute, P.O. Royal Melbourne Hospital, Victoria, Australia

NUSSENZWEI(~, VICTOR, New York University School of Medicine, Dept. of Pathology, New York, N.Y.

OPPENHEIM, JOOST, Dept. of Cell Biology, NIDR National Institutes of Health, Bethesda, Maryland 20014

OSTERLAND, C. KIRK, Washington University Medical School, Dept. of Medicine & Preven- tive Medicine, St. Louis, Missouri 63110

0STERTAG, WOLFRAM, Johns Hopkins University, School of Medicine, Dept. of Biophysics, Baltimore, Maryland 21205

OVARY, ZOLTAN, New York University School of Medicine, Dept. of Pathology, 550 First Avenue, New York, N.Y. 10016

PACHMAN, LAUR~N, La Rabida--University of Chicago Institute, Dept. of Pediatrics, 65th and Lake Michigan, Chicago, Ill. 60640

PAPERMASTER, BEN W., Dept. of Bacteriology & Immunology, University of California, Berkeley. Present address: Roswell Park Memorial Institute for Cancer Research, Buffalo, New York.

PAPER~ASTER, DAVID S., Harvard Medical School, Dept. of Pathology, 25 Shattuck Street, Boston, Mass. 02115

PAPPENHEIMER, A. M., Harvard University, Dept. of Biology, 16 Divinity Avenue, Cambridge, Mass. 02138

PARKER, DAVID, University of California, Dept. Bacteriology & Immunology, Berkeley, Cali- fornia 94720

PARK~OUSE, MICHAEL, Salk Institute for Biological Studies, San Diego, California 92112

PAUL, WrLLIAM E., New York University School of Medicine, Dept. of Pathology and Medicine, 550 First Avenue, New York, N.Y. 10099

PERHAM, RICHARD N., Yale University, Dept. of Molecular Biophysics, Box 2166, Yale Station, New Haven, Conn. 06520

PERNIS, BENVENUTO, Cattedra di Immunologia, University of Milan, Via San Barnaba 8 Milan, Italy

PETERMANN, MARY L., Sloan-Kettering Institute for Cancer Research, Dept. of Biological Chemistry, 410 East 68 Street, New York, N.Y.

PHILLIPS, R. A., Ontario Cancer Institute & University of Toronto, Dept. of Medical Biophysics, 500 Sherbourne, Toronto 5, Ontario, Canada

PIGGOT, P. J., Harvard Medical School, Dept. of Bacteriology, 25 Shattuek Street, Boston, Mass. 02215

PINCUS, JACK H., Massachusetts General Hospital, Dept. of Biochemistry--Cardiac Unit, Fruit Street, Boston, Mass. 0211

PITCHER, SUSAN, Dept. of Biochemistry, Yale University 333 Cedar Street, New Haven, Connecticut

POLZAK, ROBERTO J., Dept. of Biophysics, Johns Hopkins School of Medicine, 725 N. Wolfe St., Baltimore, Maryland 21205

POTTER, MICHAEL, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20014

POWER, BONNIE, 3 Greenleaf Street, Huntington, New York 11743

PRESS, ELIZABETH M., Dept. of Immunology, St. Mary's Hospital Medical School, London, W. 2, England

PRES~ DAVID, Roswell Park Memorial Institute, Biochemistry Research Dept., 666 Elm Street, Buffalo, N.Y. 14203

PUTNAM, FRANK W., Division of Biological Sciences, Indiana University, 120 Jordan Hall, Bloomington, Indiana

RALPH, PETER, Dept. of Biology, Massachusetts Institute of Technology, Cambridge, Mass.

RAJEWSKY, KLAUS, Institut fiir Genetik der Universitat KSln, 5 K61n-Lindenthal,Weyertal 121, Germany

RASKA, KAREL, Rutgers Medical School, Dept. of Microbiology, New Brunswick, New Jersey

READE, PETER C., Harvard Medical School, Dept. of Biology-Immunology, 25 Shattuck Street, Boston, Mass.

REISFELD, RALPH A., National Institutes of Health, Lab of Immunology, NIAID, Room 11-D-04 Bldg. 10, Bethesda, Md. 20014

REISSm, JOSE L., C. W. Post College, Greenvale, New York 11548

REVILLARD, JEAN PIERRE, New York Ufliversity Medical Center, Dept. of Medicine, 550 First Avenue, New York, N.Y. 10016

xiv LIST OF THOSE ATTENDING THE SYMPOSIUM

RICHARDS, FRANK F., Massachusetts General Hospital, Cardiac Biochemistry Laboratory, Fruit Street, Boston, Massachusetts

RImoN, ABRAHAM, New York University School of Medicine, Dept. of Medicine, 550 First Avenue, New York, N.Y. 10016

RITTENBERG, MARVIN B., University of Oregon Medical School, Dept. of Immunology, Allergy and Infections Diseases, Portland, Oregon 97201

ROlVIMEL, FRED, Dept. of Microbiology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205

ROSENBERG, DAVID, Cold Spring Harbor Lab- oratory, Cold Spring Harbor, N.Y.

RUDDLE, NANCY, Dept. of Microbiology, Yale Uni- versity, 310 Cedar Street, New Haven, Conn.

SAIFER, MARK G., University of California, Dept. Bacteriology & Immunology, Berkeley, Cali- fornia 94720

SANDBERG, ANN L., Tufts University School of Medicine, Boston, Mass.

SCHARFF, MATTHEW, Albert Einstein College of Medicine, Cell Biology and Medicine, Morris Park Ave. & Eastchester Road, Bronx New York, 10461

SCHLAMOWITZ, MAX, Sect. of Immunochemistry & Immunology, Dept. of Biochemistry, The University of Texas, M.D. Anderson Hospital & Tumor Institute, Texas Medical Center, Houston Texas 77025

SCHUBERT, DAVID, Salk Institute for Biological Studies, P.O. Box 1809 San Diego, California

SEHON, ALEC, McGill University, Lab for Bio- physical and Immunochemistry, Dept. of Chemistry, Montreal, Canada

SERCARZ, ELI E., Dept. of Bacteriology, University of California, Los Angeles, California 90024

SEUBOLD, JA~ES H., Dept. of Biology, Harvard University, Leverett G-22, Cambridge, Massachusetts

SRER, FRANKLIN ALAN, Dept. of Biology, Univer- sity of California, San Diego, La Jolla, California

SHAHN, EZRA, Hunter College, Biological Sciences Dept. 695 Park Avenue, New York, N.Y.

SHIH, AGN~S A., Dept. of Microbiology, Yale University, New Haven, Connecticut

SHIN, HYUN S., Dept. of Microbiology, Johns Hopkins Medical School, 725 N. Wolfe Street, Baltimore 5, Maryland

SIEGEL, BENJAMIN V., University of Oregon Medical School, Exp. Pathology Dept., 3181 S.W. Sam Jackson Park Road, Portland Oregon 97201

SIEGEL, JANE I . MORTON-, University of Oregon Medical School, Experimental Pathology

Dept. 3181 S.W. Sam Jackson Road, Portland, Oregon 97201

SIMINOWTCH, LouIs, The Ontario Cancer Institute and University of Toronto, 500 Sherbourne St. Dept. Medical Biophysics Toronto 5, Ontario, Canada

SIMONSEN, MORTEN, McIndoe Memorial Research Unit, Queen Victoria Hospital, East Grinstead, Sussex, England. Present address: University Institute for Exp. Immunology Norre Alle 71, Copenhagen, 0, Denmark

SINGER, S. J., Dept. of Biology, University of California at San Diego, La Jolla, California

SISKIND, GREGORY W., Dept. of Medicine, NYU Medical Center, 550 First Avenue, New York, N.Y. 10016

SJSQUIST, J., University of Umes Sweden. Present address: Wallenbcrg laboratoriet, Uppsala, Sweden

SKALKA, A. M., Genetics Research Unit, Carnegie Inst. of Wash., Cold Spring Harbor, N.Y.

SMALL, PARKER A. JR., Dept. of Microbiology, University of Florida, College of Medicine, Gainesville, Florida

SMITH, GEORGE P., Massachusetts General Hospi- tal, Cardiac Biochemistry Laboratory, Fruit St., Boston, Mass. 02114

SMITH, ROBERT L., Dept. of Biology, Brookhaven National Laboratory, Upton, New York

SMITHIES, 0., Dept. of Genetics, University of Wisconsin, Madison, Wis. 53706

SOULEIL, CLAUDE M., University of Illinois at the Medical Center, Dept. of Microbiology, Chicago, Illinois 60680

SPEIRS, ROBERT, Downstate Medical Center, 450 Clarkson Avenue, Brooklyn, New York

SPEYER, JOSErH, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York

STAVITSKY, ABRAM B., Western Reserve University School of Medicine Dept. of Microbiology, Cleveland, Ohio

STEINBERG, ROBERT A., Harvard University, Cambridge, Mass.

STERZL, J., Institute of Microbiology, Czecho- slovakian Academy of Sciences, Prague, Czechoslovakia

STONE, MARVIN J., NIAMD--National Institutes of Health, Arthritis & Rheumatism Branch, 10/9N-206, Bethesda, Maryland 20014

STONE, ROBERT L., Lilly Research Laboratories, Biological Research Division, 740 South Alabama Street, Indianapolis, Ind. 46206

SURAN, ANITA, University of California, Dept. of Bacteriology & Immunology, LSB 3570, Berkeley, California 94720

SWENSON, ROBERT M., National Institutes of Health, NIAMD, Lab of Biochemistry &

LIST OF THOSE ATTENDING THE SYMPOSIUM xv

Metabolism, Bldg. 10, Rm 9B-11, Bethesda, Maryland 20014

TALAL, NORMAN, National Institutes of Health, Arthritis Branch NIA~D, Bethesda, Mary- land 20014

TALMAGE, DAVID W., Dept. of Microbiology, University of Colorado, 4200 East 9th Avenue, Denver, Colorado 80220

TANENBAUM, STUART W., Columbia University College of Physicians & Surgeons, Dept. of microbiology, 630 W. 168 Street, New York, N.Y. 1OO32

TERRY, WILLIAM, National Cancer Institute, Immunology Branch, Bethesda, Maryland

THORBECKE, G. J., Dept. of Pathology, New York University School of Medicine, 550 First Avenue, New York, N.Y. 10016

TIDEI~AN, SUSAN, University of California, San Diego, Dept. of Biology, La Jolla, California

TILL, JAMES E., Ontario Cancer Institute, 500 Sherbourne Street, Toronto 5, Ontario, Canada

TITANI, KOITI, Indiana University, Division of Biological Sciences Bloomington, Indiana

TODD, CHARLES W., CITY of Hope Medical Center, Dept. of Biology, 1500 Duarte Road, Duarte, California 91010

T6]~ES, ZOLTAN A., Dept. of Biology, California Institute of Technology, Pasadena, California

UHR, JONATHAN W., Dept. of Medicine, New York University School of Medicine, 550 First Avenue, New York, N.Y. 10016

VALENTINE, F. T., Inf. Dis. & Immunol. Division, New York University Medical Center, 550 First Avenue, New York, N.Y. 10016

VASSALLI, P., New York University School of Medicine, Dept. of Pathology 550 First Avenue, New York, N.Y. 10016

WAKSMAN, BYRON H., Yale University, Dept. of Microbiology, New Haven, Conn. 06510

WARNER, NOEL L., The Walter & Eliza Hall Institute, Melbourne, Australia

WATSON, J. D., Biological Laboratories, Harvard University, Cambridge, Massachusetts

WAXDAL, M. J., The Rockefeller University, Dept. of Biochemistry, New York, N.Y. 10021

WEIDANZ, WILLIAM P., Hahnemann Medical College, 235 No. 15th Street, Philadelphia, Pennsylvania

WEmERT, M~RTIN, The Salk Institute for Biological Studies, P.O. Box 1809, San Diego, California

WEIGLE, WILLIAM 0., Scripps Clinic and Research Foundation, Dept. of Experimental Pathology, 476 Prospect Street, La Jolla, California

WEILER, EBERHARDT, Institute for Cancer Research, 7701 Burholme Ave., Philadelphia, Pennsylvania 19111

WEISSMAN, IRWNG L., Stanford Medical School, Dept. of Radiology, Stanford University, Stanford, California

WELTMAN, JOEL K., Brown University, Dept. of Biomedical Sciences, Providence, R.I. 02912

WERE, ZENA, The Rockefeller University, 66 Street and York Ave., New York, N.Y. 10021

WERNER, RUDOLPH, Genetics Research Unit, Carnegie Inst. of Wash., Cold Spring Harbor, New York 11724

WHITE, GORDON J., Dept. of Virology #7320, The Upjohn Company, Kalamazoo, Michigan

WIGZELL, HANS, Karolinska Institutet, Dept. of Tumor Biology, Stockholm 60, Sweden

WINCHESTER, ROBERT, Rockefeller University, Dept. of H. G. Kunkel, York Avenue and 66 Street, New York, N.Y. 10021

WoFsY, LEON, University of California, Dept. of Bacteriology & Immunology, Berkeley, Cali- fornia 94720

Wu, ALAN M., Dept. of Medical Biophysics, University of Toronto, 500 Sherbourne Street, Toronto 5, Ont., Canada

WUST, CARL J., Oak Ridge National Laboratory, Dept. of Biology, P.O. Box Y, Oak Ridge, Tennessee 37830

YAGI, YASUO, Roswell Park Memorial Institute, Dept. of Biochemistry Research, 666 Elm Street, Buffalo, New York 14203

YANC, WEN-KuANG, Biology Division, Oak Ridge National Laboratory P.O. Box Y, Oak Ridge, Tennessee 37830

YATES, RICHARD A., E. I. duPont de Nemours & Company, Central Research Dept. DuPont Experimental Station, Wilmington, Delaware

Yoo, TAI JUNE, 72 Delham Avenue, Buffalo, New York 14216

YOUNT, WILLIAM J., 33 Myrtle Avenue, Edge- water, New Jersey 07020

ZAPPACOSTA, SERAFINO, Dept. of Microbiology, 808 So. Wood Street P.O. Box 6998, Chicago, Illinois 60680

ZINDER, NORTON D., Rockefeller University, New York, N.Y. 10021

Contents Foreward . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v List of Previous Volumes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi Photographs of Some Symposium Participants . . . . . . . . . . . . . . . . . . . . . . . . . . . vii List of Those Attending the Symposium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix

INTRODUCTION

SIR MACFXaLANE BURNET. The Impac t of Ideas on Immunology . . . . . . . . . . . .

STRUCTURE OF ANTIBODIES

PUTNAM, F. W., K. TITANI, M. WIKLER and T. SHINODA: Structure and evolution of kappa and lambda light chains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9

MILSTEIN, C. B., B. FRANGIONI, and J. R. L. PINK: Studies on the variabil i ty of immunoglobulin sequence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31

APPELLA, E. and R. M. PERHAM : Structure of immunoglobulin light cha ins . . . 37 PRESS, E. M. and P. J . PIOGOT: The chemical structure of the heavy chain of

human immunoglobulin G . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 WAXDAL, M. J., W. H. KONIGSBERG and G. M. EDELMAN: The structure of a

human gamma G immunoglobulin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 CEBRA, J . J. : Common peptides comprising the N-terminal half of heavy chain

from rabbit=IgG and specific antibodies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65 EISEN, H. N., J. R. LITTLE, C. K. OSTERLAND and E. S. SIMMS: A myeloma

protein with ant ibody activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 STONE, M. J. and H. METZGER: The valence of a Waldenstrom macroglobulin

ant ibody and further thoughts on the significance of paraprotein antibodies 83 NIZONOFF, A., S. ZAPPACOSTA and R. JUREZIZ: Properties of crystallized rabbit

anti-P azobenzoate ant ibody . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 POLJAK R. J., D. J. GOLDSTEIN, n . L. HUMPHREY and H. M. DINTZlS: Crystallo-

graphic studies of rabbit and human Fc fragments . . . . . . . . . . . . . . . . . . . . 95 SINOER, S. J., L. I. SLOBIN, N. O. THORPE and J. W. FENTON, I I : On the

structure of ant ibody active sites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99 WOFSY, L. and D. C. PARKER: Comparative studies of ant ibody active sites. . 111 Yoo, T. J. , O. A. ROHOLT, and D. PRESSMAN: Hapten binding activity in isolated

light polypeptide chains from rabbit ant ibody . . . . . . . . . . . . . . . . . . . . . . . . 117 KOSHLAND, M. E. : Location of specificity and allotypic amino acid residues in

ant ibody Fd fragments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 HAMERS, R. and C. HAMERS-CASTERMAN: Evidence for the presence of the Fc

allotypic marker As8 and the Fd allotypic marker Asl in the same molecules of rabbit IgG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

EVOLUTION AND GENETICS OF ANTIBODIES

HOOD, L., W. R. GRAY, B. G. SANDERS and W. J . DREYER: Light chain evolution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133

BAGLIONI, C., D. CIOLI, G. GORINI, A. RUFFILLI and L. ALESCIO-ZONTA: Studies on fragments of light chains of human immunoglobulins: Genetic and biochemical implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147

SMITHIES, 0.: The genetic basis of antibody variability . . . . . . . . . . . . . . . . . . . . 161 CRICK, F. H. C., L. HOOD, O. SMITHIES, W. J. DREYER, C. MILSTEIN, B.

PAPERMASTER, N. A. MITCHISON, J. J. CEBRA, D. W. TALMAGE, C. BAGLIONI, G. EDELMAN, N. JERNE: General discussion on theories of antibody variability . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169

NATWO, J. B., H. G. KUNKEL and S. P. LITWIN: Genetic markers of the heavy chain subgroups of human gamma G globulin . . . . . . . . . . . . . . . . . . . . . . . . . 173

xvii

xviii CONTENTS

HERZE:NBERG, L. A., J. D. MI:NNA and L. A. HERZENBERG: The chromosome region for immunoglobulin heavy chains in the mouse: allelic electrophoretic mobility differences and allotype suppression . . . . . . . . . . . . . . . . . . . . . . . . . 181

POTTER, M. and R. LIEBERMA:N: Genetic studies of immunoglobulins in m ice . . 187 MAGE, R. G. : Quantitative studies on the regulation of expression of genes for

immunoglobulin allotypes in heterozygous rabbits . . . . . . . . . . . . . . . . . . . . . 203

SYNTHESIS OF ANTIBODIES

CoHNN, M. : Natural history of the myeloma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 ASKO:NAS, B. A. and A. R. WmLIAMSONN: Biosynthesis and assembly of immuno-

globulin G . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223 FLEISCH~A:N, J. B. : Synthesis of the rabbit gamma G heavy chain . . . . . . . . . . 233 SCHARFF, M. D., A. L. SHAPIRO and B. GI:NSBERG: The synthesis, assembly and

secretion of gamma globulin polypeptide chains by cells of a mouse plasma cell tumor . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235

GREE:NB ERG, L. J. and J. W. UHR: DNA-RNA hybridization studies of immuno- globulin synthesizing tumors in mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243

LENN:Nox, E. S., P. M. K:NOI"F, A. J. MUNRO and R. M. E. PARF~HOUSE: A search for biosynthetic subunits of light and heavy chains of immunoglobulins.. 249

MELCHERS, :F. and P. M. K:NOPF: Biosynthesis of the carbohydrate portion of immunoglobulin chains: Possible relation to secretions . . . . . . . . . . . . . . . . . 255

MOROZ, C. and J. W. UHR: Synthesis of the carbohydrate moiety of gamma globulin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263

KERN, M. and R. M. SWE:NSO:N: Biochemical studies of the intracellular events involved in the secretion of gamma globulin . . . . . . . . . . . . . . . . . . . . . . . . . . 265

MACH, B., H. KOBLET and D. GROSS: Biosynthesis of immunoglobulin in a cell- free system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269

RALPH, P., M. BECKER and A. RICH: Immunoglobulin synthesis in a cell-free system . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277

FAHEY, J. L. and I. FI:NEGOLD: Synthesis of immunoglobulins in human lymphoid cell lines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283

REISFELD, R. A.: Heterogeneity of rabbit light-poly peptide chains . . . . . . . . . . 291 HABER, E., F. F. RICHARDS, J. SPRAGG, K. F. AUSTE:N, M. VALLOTTO:N and

L. B. PAGE: Modifications in the heterogeneity of the antibody response . . 299 Du~IsKI, S.: Synthesis of allotypically defined immunoglobulins in rabbits . . . . 311 CHOU, C. T., B. CINADER, and S. DUBISKI: Quantitative studies of antibody

production by plaque-forming cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 PER:NIS, B. : Relationships between the heterogeneity of immunoglobulins and

the differentiation of plasma cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 FISHMA:N, M. and F. L. ADLER: The role of macrophage--RNA in the immune

response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 343 COHE:N, E. P. and K. RASKA: Antigen--unique species of RNA in peritoneal cells

of mice which do not adhere to glass . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 DREYER, W. J., W. R. GRAY, and L. HOOD: The genetic, molecular, and cellular

basis of antibody formation: some facts and a unifying hypothesis . . . . . . . 353

DIFFERENTIATION AND CELLULAR EVENTS

NOSSAL, G. J. V., K. D. SHORTMAN, J. F. A. P. MILLER, G. F. MITCHELL, and J. S. HASKILL: The target cell in the induction of immunity and tolerance 369

ADA, G. L., C. R. PARRISH, G. J. V. NOSSAL, and A. ABBOT: The tissue localiz- ation, immunogenic, and tolerance-inducing properties of antigens and antigen-fragments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381

ELLIS, S. T., J. L. GOWANS and J. C. HOWARD: Cellular events during the formation of antibody . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 395

DUTTON, R. W. and R. I. MISHELL: Cellular events in the immune response. The in vitro response of normal spleen cells to erythrocyte antigens . . . . . . . . . 407

CONTENTS xix

FELDMAN, M. and R. GALLILY: Cell interactions in the induction of ant ibody formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415

M~KELA, 0.: The specificities of antibodies produced by single cells . . . . . . . . . . 423 MITCHISON, N. A. : Antigen recognition responsible for the induction in vitro of

the secondary response . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431 GELL, P. G. H.: Restrictions on antibody production by single cells . . . . . . . . . 441 PAPERMASTER, B. W. : The clonal differentiation of antibody-producing cells . . 447 TILL, J. E., E. A. MCCULLOCH, R. A. PHILLn'S and L. SIMINOWTCH: Analysis

of differentiating clones derived from marrow . . . . . . . . . . . . . . . . . . . . . . . . . 461 BUSSARD, A. E. : Pr imary antibody response induced in vitro among cells from

normal animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465 LITT, M. : Studies of the latent period. I. Pr imary ant ibody in guinea pig lymph

nodes 7�89 minutes after introduction of chicken erythrocytes . . . . . . . . . . . . 477 STERZL, J. : Factors determining the differentiation pathways of immuno-

competent cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493 WIGZELL, T.: Studies on the regulation of antibody synthesis . . . . . . . . . . . . . . . 507 SIMONSEN, M.: The clonal selection hypothesis evaluated by grafted cells

reacting against their hosts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 517 FAZEKAS, S. de ST. GROTH: Cross recognition and cross reactivity . . . . . . . . . . . 525 SELA, M., B. SCHECHTER, I. SCHECHTER, and F. BOREK: Antibodies to sequential

and conformational determinants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537 RAJEWSKY, K. and E. ROTTLANDER: Tolerance specificity and the immune

response to lactic dehydrogenase isoenzymes . . . . . . . . . . . . . . . . . . . . . . . . . . 547 WEIGLE, W. 0. and E. S. GOLUB : Kinetics of the establishment of immunological

unresponsiveness to serum protein antigens . . . . . . . . . . . . . . . . . . . . . . . . . . . 555 HAUROWITZ, F.: Evolution of selective and instructive theories of ant ibody

formation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559 BENACERRAF, B., I. GREEN, and W. E. PAUL: The immune response of guinea

pigs to hapten-poly-L-lysinc conjugates as an example of the genetic control of the recognition of antigenicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 569

SJOQUIST, J., A. FORSGREN, G. T. GUSTAFSON, and G. STALENHEIM: Biological importance of the Fc-region of gamma globulins . . . . . . . . . . . . . . . . . . . . . . 577

METCALF, D. : Relation of the thymus to the formation of the immunologically reactive cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583

SUMMARY

JERNE, N. K.: Waiting for the End . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 591