Mode of Bioenergetic Metabolism during B Cell Differentiation in the Intestine Determines the Distinct Requirement for Vitamin B1

•Naive B cells and IgA+ PCs use non-glycolytic- and glycolysis-TCA axis, respectively•Vitamin B1 depletion impairs TCA cycle activity•Vitamin B1 depletion decreases naive B cells without affecting IgA+ PCs•Vitamin B1 depletion impairs initiation of antigen-specific antibody responses

SummaryBioenergetic metabolism varies during cell differentiation, but details of B cell metabolism remain unclear. Here, we show the metabolic changes during B cell differentiation in the intestine, where B cells differentiate into IgA+ plasma cells (PCs). Naive B cells in the Peyer’s patches (PPs) and IgA+ PCs in the intestinal lamina propria (iLP) both used the tricarboxylic acid (TCA) cycle, but only IgA+ PCs underwent glycolysis. These metabolic differences reflected their dependencies on vitamin B1, an essential cofactor for the TCA cycle. Indeed, the diminished activity of the TCA cycle after dietary vitamin B1 depletion decreased the number of naive B cells in PPs without affecting IgA+ PCs in the iLP. The maintenance of naive B cells by dietary vitamin B1 was required to induce—but not maintain—intestinal IgA responses against oral antigens. These findings reveal the diet-mediated maintenance of B cell immunometabolism in organized and diffuse intestinal tissues.

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