title: Mode of Bioenergetic Metabolism during B Cell Differentiation in the Intestine Determines the Distinct Requirement for Vitamin B1.
abstract: 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.
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Graduate School of Medicine, Graduate School of Pharmaceutical Sciences and Graduate School of Dentistry, Osaka University, Osaka 565-0871, Japan; Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: kunisawa@nibiohn.go.jp.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, and Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Tokyo 160-8582, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PREST), Tokyo 102-8666, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sugiura
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Taichi
authors.initials: T
authors.lastname: Wake
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nagatake
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan.
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Nagasawa
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Shikata
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, and Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Tokyo 160-8582, Japan; Japan Science and Technology Agency (JST), Precursory Research for Embryonic Science and Technology (PREST), Tokyo 102-8666, Japan.
authors.forename: Kurara
authors.initials: K
authors.lastname: Honda
authors.affiliation: Laboratory of Vaccine Materials, National Institutes of Biomedical Innovation, Health and Nutrition, Osaka 567-0085, Japan; Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Hashimoto
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Cell Biology and Anatomy and Medical Photonics Research Center System Molecular Anatomy, Hamamatsu University School of Medicine, Shizuoka 431-3192, Japan; The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Department of Anatomy, The University of Hong Kong, Pok Fu Lam, Hong Kong.
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Setou
authors.affiliation: Department of Biochemistry, Keio University School of Medicine, and Japan Science and Technology Agency (JST), Exploratory Research for Advanced Technology (ERATO), Suematsu Gas Biology Project, Tokyo 160-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.affiliation: Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; Japan Science and Technology Agency (JST), Core Research for Evolutional Science and Technology (CREST), Tokyo 102-0076, Japan; Department of Medical Genome Science, Graduate School of Frontier Science, The University of Tokyo, Chiba 277-8562, Japan; Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage / Q000276:immunology; D002952:Citric Acid Cycle / Q000276:immunology; D005260:Female; D006019:Glycolysis / Q000276:immunology; D056724:Immunity, Humoral; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008807:Mice, Inbred BALB C; D010581:Peyer's Patches / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D010950:Plasma Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D013831:Thiamine / Q000276:immunology / Q000378:metabolism*; D014804:Vitamin B Deficiency / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000906:Antibodies; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D013831:Thiamine