Alternate pathways for Bcl6-mediated regulation of B cell to plasma cell differentiation

Abstract

AbstractThe transcription factor Bcl6 regulates germinal center formation and differentiation of B cells into high‐affinity antibody‐producing plasma cells. The direct double‐negative regulatory circuit between Bcl6 and Blimp‐1 is well established. We now reveal alternative mechanisms for Bcl6‐mediated regulation of B‐cell differentiation to plasma cells and show with DT40 cells that Bcl6 directly promotes the expression of Bach2, a known suppressor of Blimp‐1. Moreover, Bcl6 suppresses Blimp‐1 expression through direct binding to the IRF4 gene, as well as by promoting the expression of MITF, a known suppressor of IRF4. We also provide evidence that Bcl6 is needed for the expression of AID and UNG, the indispensable proteins for somatic hypermutation and class‐switch recombination, and UNG appears to be a direct Bcl6 target. Our findings reveal a complex regulatory network in which Bcl6 acts as a key element dictating the transition of DT40 B cells to plasma cells.