BLIMP1 controls GC B cell expansion and exit through regulating cell cycle progression and key transcription factors...

In B cells, BLIMP1 is required for plasma cell differentiation. BLIMP1 is also expressed in some germinal center (GC) B cells (GCBC), yet the role of BLIMP1 in GCBC is not understood. Here we generated mixed bone marrow (BM) chimeric mice using Prdm1^+/+ CD19^Cre and Prdm1^fl/fl CD19^Cre BM, allowing us to examine the cell-intrinsic functions of BLIMP1 in GCBC, independent of antibody or antigen levels. Strikingly, BLIMP1-deficient B cells quickly dominate GCs and persist for a much longer time compared with wild-type cells. BLIMP1 deficiency promotes positive selection of GCBCs and enhances cell-cycle progression. Additionally, BLIMP1 deficiency alters class switching and memory B cell generation from GCBCs. Mechanistically, BLIMP1-deficient GCBCs fail to downregulate BCL6 and to upregulate IRF4, indicating that BLIMP1 controls the expression of these transcription factors that mediate exit from the GC. These studies revealed unique functions of BLIMP1 in regulating GCBC responses that impact long-lived immune compartments.