摘要:SummaryWhile diet modulates immunity, its impact on B cell ontogeny remains unclear. Using mixture modeling, a large-scale isocaloric dietary cohort mouse study identified carbohydrate as a major driver of B cell development and function. Increasing dietary carbohydrate increased B cell proportions in spleen, mesenteric lymph node and Peyer’s patches, and increased antigen-specific immunoglobulin G production after immunization. This was linked to increased B lymphopoiesis in the bone marrow. Glucose promoted early B lymphopoiesis and higher total B lymphocyte numbers than fructose. It drove B cell development through glycolysis and oxidative phosphorylation, independently of fatty acid oxidationin vitroand reduced B cell apoptosis in early development via mTOR activation, independently of interleukin-7. Ours is the first comprehensive study showing the impact of macronutrients on B cell development and function. It shows the quantitative and qualitative interplay between dietary carbohydrate and B cells and argues for dietary modulation in B cell-targeting strategies.Graphical abstractDisplay OmittedHighlights•Dietary carbohydrates dynamically drive B cell lymphopoiesis and increase splenic B cells•Dietary glucose, but not fructose, affects B cell lymphopoesis•Dietary carbohydrates activate mTOR in B cells, particularly in early progenitors•Dietary carbohydrates increase plasma B cells and IgG response in immunized miceBiological sciences; Immunology; Cell biology; Developmental biology