CHAITRALI. VIVEK. JADHAVROLL NO:- 07

PAPER:- 2

Antibody gene rearrangement

OBJECTIVES: Antibody- structure and properties Genetic organisation Genetic rearrangement Antibody diversity

MOLECULAR BASIS OF ANTIBODY DIVERSITY:~

Glycoprotein.Produced by plasma cells.Recognize & bind antigens.Leads to:

PhagocytosisComplement activationAntibody dependent cell cytotoxicity (ADCC).

ANTIBODY

ANTIBODY STRUCTURE

Opsonization. Immune Adherence. Transcytosis. Complement Activation. Virus and Toxin Neutralization. Antibody-Mediated Cellular Cytotoxicity. Direct lysis of Microbes.

FUNCTIONS OF ANTIBODY

Located on different chromosomes for different chains:

H-chain gene family on Ch 14.Kappa light chain gene family on Ch 2.Lambda light chain gene family on Ch 22.

One family multiple gene segments for variable region.

One gene segment multiple genes for same specific region.

IMMUNOGLOBULIN GENE FAMILIES IN HUMAN:~

Encoded by 3 genes:V (variable gene) J (joining gene)C (constant gene)

V & J together code for variable region ( VL). C gene codes for the constant region ( CL).A complete L chain formed by splicing of V, J & C

genes.

LIGHT CHAIN GENES:

Encoded by 4 genes:Variable region coded by 3 genes:

VH (variable)JH (joining)DH (diversity)

Constant region (CH) encoded by one single gene.

H-chain C-segment has 9 genes.

HEAVY CHAIN GENES:

One that occurs at DNA level. Another that occurs at RNA level.

GENE REARRANGEMENT

V,D & J joining in H-chains; V & J joining in L-chains.C region genes remain separated from V-region gene

by J genes and intron.A primary RNA transcript is generated.Only Cμ & Cδ genes are transcribed in naïve B cells.The other C region genes transcribed during class

switching.

REARRANGEMENT AT DNA LEVEL:

Takes place during the primary RNA transcript processing.

The C-region gene spliced with V-region genes to generate complete H & L chain genes.

Plays crucial role in:Production of membrane bound Ab.Production of secreted form of Ab.Production of different classes of Ab.

REARRANGEMENT AT RNA LEVEL:

Rearranged V region at DNA level contains the following sequences from 5’ end to 3’ end:

L-exon of joined VH gene.VHDHJH –combined exon. Intron between L & VHDHJH. Intron 3’ to J gene.Remaining JH genes, if any, followed by complete set of CH

region genes.

HEAVY-CHAIN GENE REARRANGEMENT:

The rearranged H-gene is transcribed.Next rearrangement at RNA level takes place.Differential splicing of the primary RNA transcript leads to generation of mRNA for both μ and δ heavy chains.

After translational, leader peptide is cleaved to produce a fully functional chain.

Occurs after the rearrangement in heavy chain.

Similar in pattern.No D-genes involved.

Variable region rearrangement in DNA.Splicing with C-region gene during RNA processing.

LIGHT-CHAIN REARRANGEMENT:

Immunology, 5th edition, by kuby. Textbook of basic and clinical immunology – by Sudha

Gangal & Shubhangi Sontakke. www.slideshare.com https://www.youtube.com/watch?v=chwXp564-6o

REFERENCES:~

THANK YOU!!