When Do Isotypes When Do Isotypes Matter?Matter?

The primary -> secondary immune response:

•Increase Ig titer

•Switch from IgM to IgG

•Increase Ag binding affinity

Where and when do affinity Where and when do affinity maturations and isotype class switch maturations and isotype class switch

occur??occur??

BCR:mIgMBCR:mIgM sIgGsIgGmIgGmIgG

CSR/SHM

Infection and Ag presentationInfection and Ag presentation

Infection and Ag presentationInfection and Ag presentation

Infection and Ag presentationInfection and Ag presentation

T cell zone

B cell zone

Red pulp border

Generation of Generation of plasmablastsplasmablastsin the spleenin the spleen

T cells: CD4+ and CD8+T cells: CD4+ and CD8+

CD8+

CD4+

APCs: present Ag in the context APCs: present Ag in the context of MHC class II to T helper cellsof MHC class II to T helper cells

Ag presentation to T helper cells Ag presentation to T helper cells in the spleenin the spleen

T helper cells are CD4+T helper cells are CD4+

•are activated by APCare activated by APC

•secrete cytokines tosecrete cytokines toaugment the immuneaugment the immuneresponse response

T helper cells polarizeT helper cells polarize into Tinto THH1 and T1 and THH2 cells2 cells

and secrete uniqueand secrete unique combinations of combinations of cytokinescytokines

Cytokines target germline transcripts Cytokines target germline transcripts to specific Ig isotypes in B cellsto specific Ig isotypes in B cells

Cytokines target germline transcripts Cytokines target germline transcripts to specific isotypes to specific isotypes

33 2b2b

T cell zoneB cell zone

Red pulp border

Germinal Center

SHM Occurs in SHM Occurs in the Germinal the Germinal

Center B CellsCenter B Cells

Primary focus

SHM Occurs in Germinal Center B CellsSHM Occurs in Germinal Center B Cells

T cell zone

Red pulp border

Germinal Center

Primary focus

plasmablasts

T cell zone

sIgM sIgM and sIgG