Human B cell differentiation pathways of multiple effector subsets. When naïve B cells receive signals via the BCR or T cell help in the form of CD40L and cytokines, they can either develop into short-lived plasmablasts secreting predominantly IgM, or form GCs, which give rise to long-lived MBCs and PCs capable of secreting IgM, IgG, and IgA. Activated B cells can also acquire expression of the transcription factor T-bet to differentiate into CD11c⁺CD21^loT-bet⁺ B cells. CD11c⁺CD21^loT-bet⁺ B cells can likely arise from naïve/extrafollicular, GC, or MBCs. Several subsets of CD11c⁺CD21^loT-bet⁺ B cells have been identified based on distinct phenotypes and disease states, as indicated. Whether these subsets represent precursor/progeny remains to be determined. CD11c⁺CD21^loT-bet⁺ B cells are enriched for production of autoAbs and can also present autoAg to CD4⁺ T cells to initiate activation of other autoreactive B cells. CVID: common variable deficiency; SLE: systemic lupus erythematosus; HIV: human immunodeficiency virus; MS: multiple sclerosis; RA: rheumatoid arthritis; TME: tumor microenvironment.