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

Highlights

• 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

Summary

Bioenergetic 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.