Bach2 is a critical negative regulator of Tfh cell differentiation

T follicular helper (Tfh) cells are essential for germinal center B cell responses; however, the molecular mechanism underlying Tfh cell programming, in particular, the initial Tfh cell development, remains largely unknown. Here, we show that in vivo, despite enhanced non-Tfh effector functions, the deletion of transcription factor Bach2 still 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 identified a novel regulatory element in the murine CXCR5 locus that negatively regulates CXCR5 promoter activities in a Bach2-dependent manner. Furthermore, we find that Bach2 is also essential for CD4+ T cell memory including Tfh cell memory. These results demonstrate that Bach2 is a novel critical player in controlling Tfh cell responses. Transcriptome analysis of naive OT-II Bach2-WT and OT-II Bach2-conditional knockout (cKO), and ex vivo OT-II Bach2-WT and Bach2-cKO donor cells 3 days after immunization.