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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\u2013ligand 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\u2013dependent but GC Tfh\u2013independent manner. 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