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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