BCL6 is required for the development of functionally responsive IgM+ GC Tfh independent Memory B Cells

Humoral immunity depends upon long-lived, antibody-secreting plasma cells and memory B cells (MBCs). MBCs exhibit significant phenotypic and functional heterogeneity shaped by interactions with CD4+ T cells. It is currently unclear how specific CD4+ T cell interactions with B cells influence specific MBC subset generation. We used genetic ablation and antibody depletion to dissect key CD4+ T cell/B cell receptor-ligand pair interactions to define critical signals that govern the development of specific MBC populations. While it has previously been suggested that CD73+CD80+ MBCs are derived from the germinal center (GC), we show that highly functional CD73+CD80+ IgM+ MBCs differentiate in a BCL6 and CD4+ T cell-dependent, but GC Tfh-independent manner. BCL6 upregulation, in the presence or absence of a GC, can therefore serve as a predictor of long-lived, functional MBCs. This data is an annotated B cell receptor (BCR) sequencing table from bulk sorted B cells of different gated populations from knockout and wild type mice. BCRs sequences were reconstructed from Illumina 150x2 paired end read sequencing reads with the TRUST4 software for each UMI after barcode correction using UMI-tools. Libraries were created with a smart-seq approach that attached a random UMI template-switch oligo (TSO) to each transcript, and then BCRs specifically amplified in a multiplex approach using a TSO primer with C-gene primers.