Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells

• DOI: 10.1038/s41467-022-29426-x
• Publication Date: 2022-04-04T10:04:51Z
• Authors: Davide G. Franchina; Henry Kurniawan; Melanie Grusdat; Carole Binsfeld; Luana Guerra; Lynn Bonetti; Leticia Soriano-B...; Anouk Ewen; Takumi Kobayashi; Sophie Farinelle; Anna Rita Minafra; Niels Vandamme; Anaïs Carpentier; Felix K. Borgmann; Christian Jäger; Ying Chen; Markus Kleinewiet...; Vasilis Vasiliou; Michel Mittelbronn; Karsten Hiller; Philipp A. Lang; Dirk Brenner
• Keywords: 0301 basic medicine; Lymphoid Tissue; Science; Glutamate-Cysteine Ligase; Article; MECHANISMS; ACTIVATION; Mice; 03 medical and health sciences; RESPIRATORY ENZYMES; OXIDATIVE-PHOSPHORYLATION; Medicine and Health Sciences; Lymphoid Tissue/metabolism; Animals; B-Lymphocytes; REVERSIBLE OXIDATION; B1B CELLS; VIRAL PERSISTENCE; Q; GLYCOPROTEIN; Biology and Life Sciences; Glutathione; Glutathione/metabolism; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; 3. Good health; BUTHIONINE SULFOXIMINE; Oxidation-Reduction

The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB MZB, respectively) are not well understood. Here we show, by studying mice with cell-specific ablation of catalytic subunit glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis differentiation MZB to a larger extent than FoB, while glutathione-dependent redox control contributes dependencies FoB. Specifically, Gclc in FoB induces features wild-type such as increased ATP levels, glucose metabolism, mTOR activation, protein synthesis. Furthermore, Gclc-deficient have block mitochondrial electron transport chain (ETC) due diminished complex I II activity thereby accumulate tricarboxylic acid cycle metabolite succinate. Finally, deficiency hampers activation antibody responses vitro vivo, susceptibility viral infections. Our results thus suggest is required ensure development ETC integrity efficacy antiviral humoral immunity.