T-bet controls the maintenance and differentiation potential of flu-induced effector memory B cells

Abstract Although the transcription factor (TF) T-bet is expressed by antigen-experienced human B cells, including extrafollicular IgD negCD27 negmemory-like DN2 cells and +effector memory (eBmem), it unknown whether expression influences development, maintenance, or function of Bmem cells. Using oligo-labeled recombinant influenza nucleoprotein (NP) tetramers paired single cell RNA V(D)J sequencing, we characterized NP-specific in draining LN flu-infected mice. We identified 7 transcriptionally distinct clusters mature non-replicating β While none TFs required for plasma (PC) lineage commitment, one cluster, containing clonally-expanded somatically-mutated significantly higher levels gene, Tbx21, was very similar to +eBmem. The NP +Tbx21 +Bmem upregulated gene networks associated with metabolic reprogramming, protein synthesis mTOR-dependent unfolded response, suggesting that these might represent are metabolically poised rapid PC differentiation. constitutive inducible models delete Tbx21 specifically showed differentiation potential controlled development persistence +eBmem subsets lung. Thus not only marks effector but also regulates flu-induced provide humoral protection from infection. Supported a grant NIH (R01 AI110508)