Dietary carbohydrate, particularly glucose, drives B cell lymphopoiesis and function
Jian Tan,
Duan Ni,
Jibran Abdul Wali,
Darren Anthony Cox,
Gabriela Veronica Pinget,
Jemma Taitz,
Claire Immediato Daïen,
Alistair Senior,
Mark Norman Read,
Stephen James Simpson,
Nicholas Jonathan Cole King,
Laurence Macia
Affiliations
Jian Tan
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Physiology, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
Duan Ni
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Physiology, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
Jibran Abdul Wali
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia
Darren Anthony Cox
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Pathology School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
Gabriela Veronica Pinget
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Physiology, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
Jemma Taitz
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Physiology, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia
Claire Immediato Daïen
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; CHRU Montpellier, Département de Rhumatologie, Montpellier FRANCE & University of Montpellier, PhyMedExp, INSERM, CNRS UMR, Montpellier, France
Alistair Senior
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Computer Science, Faculty of Engineering, University of Sydney, Sydney, NSW, Australia; School of Mathematics and Statistics, University of Sydney, Sydney, NSW, Australia
Mark Norman Read
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Computer Science, Faculty of Engineering, University of Sydney, Sydney, NSW, Australia; The Westmead Initiative, Faculty of Engineering, The University of Sydney, Sydney, NSW, Australia
Stephen James Simpson
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia
Nicholas Jonathan Cole King
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Pathology School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Sydney Cytometry, The University of Sydney and The Centenary Institute, Sydney, NSW, Australia; Corresponding author
Laurence Macia
Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; Discipline of Physiology, School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia; Corresponding author
Summary: While 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 oxidation in vitro and 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.
