GSE184846
Dependence on Bcl6 and Blimp1 identifies distinct mechanisms driving memory and follicular helper CD4+ T cell differentiation [scATAC-Seq]
During the immune response, CD4+ T cells differentiate into distinct effector subtypes, including follicular helper T (Tfh) cells that help B cells, and into memory cells. Tfh and memory cells are required for long-term immunity; both depend on the transcription factor Bcl6, raising the question of whether they differentiate through similar mechanisms. Here, using notably single-cell RNA and ATAC sequencing, we show that virus-responding CD4+ T cells lacking both Bcl6 and Blimp1 can differentiate into cells with transcriptomic, chromatin accessibility and function attributes of memory cells, but not of Tfh cells. Thus, Bcl6 promotes memory cell differentiation primarily through its repression of Blimp1.  These findings demonstrate that distinct mechanisms underpin the differentiation of memory and Tfh CD4+ cell and define the Bcl6-Blimp1 axis as a potential target for promoting long-term memory T cell differentiation. Overall design: Single cell epigenomic analysis of d7, >=d30 p.i. WT and dKO GP66-I-Ab+ CD4+ T cells and d7 p.i. WT and dKO Smarta T cells