Spatiotemporal dynamics of Bach2 orchestrates B cell responses and fate decision II

The molecular circuits that direct early T-dependent B cell responses and alternative cell-fate decisions remain poorly understood. Here, we show that either B cell receptor (BCR) or CD40 signals promoted mTORC1-dependent translation of the transcription factor Bach2. Transient up-regulation of Bach2 protein restrained activated B cell expansion and differentiation into plasma cell while promoting the germinal center (GC) and memory B cell fates at the pre-GC stage. However, enforced Bach2 expression facilitated memory B cell generation versus other cell fates. Mechanistically, Bach2 limited access of AP-1 factors and formed a reciprocal repression loop with IRF4. BCR and CD40 signals also down-regulated Bach2 transcript in antigen-activated B cells, and diversified its abundance in various effector populations, predisposing Bach2 protein expression and subsequent cell-fate choices during memory recall and GC reaction. Thus signaling-induced differential dynamics of Bach2 protein and mRNA in activated B cell control their cell-fate outcomes and imprint the fate of their descendant effector cells. NP-specific naïve B cell（CD19+IgD+）was sorted at day0,and NP-specific plasma cell(IgD-CD19-CD138+),memory B cell(CD19+IgD-GL7-CD38+),germianl center B cell(CD19+IgD-GL7+CD38-) and active precursor B cell(CD19+IgD-GL7+CD38+) were sorted at day 5 after immunization and subjected for transcriptional profile analysis