Fig. 1.
IRF4-graded expression in mature B cells during germinal center reaction. After antigen engagement, mature B cells initiate the germinal center reaction where proliferating centroblasts are regulated by high expression levels of BCL6, PAX5 and AID but low levels of IRF4. Reduced IRF4 levels also favor the localization of cycling B cells in the dark zone by regulating CXCR4 expression. Following antigen affinity maturation, IRF4 levels are progressively increased favoring class-switch recombination (CSR), mobilization of B cells to the light zone, and plasma cell (PC) differentiation. High IRF4 levels activate the PC transcriptional program by lowering BCL6 and inducing BLIMP1 and XBP1. Abbreviations: SHM, somatic hypermutation; CSR, class-switch recombination; FDC, follicular dendritic cells; PC, plasma cells; GC, germinal center; Tfh: follicular helper T cells