Bach2 negatively regulates Tfh cell differentiation and is critical for CD4+ T cell memory

T follicular helper (Tfh) cells are essential for germinal center B cell responses. The molecular mechanism underlying the initial Tfh cell differentiation, however, is still incompletely understood. Here, we show that in vivo , despite enhanced non-Tfh effector functions, the deletion of transcription factor Bach2 results in preferential Tfh cell differentiation. Mechanistically, the deletion of Bach2 leads to the induction of CXCR5 expression even before the up-regulation of Ascl2. Subsequently we have identified a novel regulatory element in the murine CXCR5 locus that negatively regulates CXCR5 promoter activities in a Bach2-dependent manner. Bach2-deficiency eventually results in a collapsed CD4 + T cell response with severely impaired CD4 + T cell memory including Tfh cell memory. Our results demonstrate that Bach2 critically regulates Tfh cell differentiation and CD4 + T cell memory.