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Significance The functions of transcription factors IRF8 and PU.1 in B cell activation and differentiation have been poorly understood due to redundancy between the family members. By usingMb1 -Cre–mediated B cell-specific deletion ofIrf8 andSpi1 (encoding PU.1), we provide evidence here that (i ) double deletion of IRF8 and PU.1 resulted in severe deficiency in follicular and germinal center B cells; (ii ) antibody affinity maturation was compromised in double-mutant mice; and (iii ) the expression of BCL6 was dependent on IRF8 and PU.1, indicating the existence of an IRF8/PU.1–BCL6 axis in the initiation phase of the germinal center response. Our data thus reveal that IRF8 and PU.1 are indispensable for the development of late-stage B cells.

Transcription factors IRF8 and PU.1 are required for follicular B cell development and BCL6-driven germinal center responses