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Title: | Glutathione-dependent redox balance characterizes the distinct metabolic properties of follicular and marginal zone B cells | Authors: | Franchina, Davide G. Kurniawan, Henry Grusdat, Melanie BINSFELD, Carole Guerra, Luana Bonetti, Lynn Soriano-Baguet, Leticia Ewen, Anouk Kobayashi, Takumi Farinelle, Sophie Minafra, Anna Rita Vandamme, Niels CARPENTIER, Anais Borgmann, Felix K. Jager, Christian Chen, Ying KLEINEWIETFELD, Markus Vasiliou, Vasilis Mittelbronn, Michel Hiller, Karsten Lang, Philipp A. Brenner, Dirk |
Issue Date: | 2022 | Publisher: | NATURE RESEARCH | Source: | Nature Communications, 13 (1) (Art N° 1789) | Abstract: | The metabolic principles underlying the differences between follicular and marginal zone B cells (FoB and MZB, respectively) are not well understood. Here we show, by studying mice with B cell-specific ablation of the catalytic subunit of glutamate cysteine ligase (Gclc), that glutathione synthesis affects homeostasis and differentiation of MZB to a larger extent than FoB, while glutathione-dependent redox control contributes to the metabolic dependencies of FoB. Specifically, Gclc ablation in FoB induces metabolic features of wild-type MZB such as increased ATP levels, glucose metabolism, mTOR activation, and protein synthesis. Furthermore, Gclc-deficient FoB have a block in the mitochondrial electron transport chain (ETC) due to diminished complex I and II activity and thereby accumulate the tricarboxylic acid cycle metabolite succinate. Finally, Gclc deficiency hampers FoB activation and antibody responses in vitro and in vivo, and induces susceptibility to viral infections. Our results thus suggest that Gclc is required to ensure the development of MZB, the mitochondrial ETC integrity in FoB, and the efficacy of antiviral humoral immunity. Follicular and marginal zone B (FoB and MZB, respectively) cells have divergent metabolic characteristics. Here the authors show that deficiency of glutamate cysteine ligase (Gclc), the enzyme for glutathione synthesis, differentially impacts FoB and MZB homeostasis, while specifically impeding FoB activation and downstream antiviral immunity. | Notes: | Brenner, D (corresponding author), Luxembourg Inst Hlth, Dept Infect & Immun, Expt & Mol Immunol, Esch Sur Alzette, Luxembourg.; Brenner, D (corresponding author), Univ Luxembourg, Luxembourg Ctr Syst Biomed, Immunol & Genet, 7Ave Hauts Fourneaux, Esch Sur Alzette, Luxembourg.; Brenner, D (corresponding author), Univ Southern Denmark, Odense Univ Hosp, Odense Res Ctr Anaphylaxis ORCA, Dept Dermatol, Odense, Denmark.; Brenner, D (corresponding author), Univ Southern Denmark, Odense Univ Hosp, Allergy Ctr, Odense, Denmark. dirk.brenner@lih.lu |
Keywords: | Animals;B-Lymphocytes;Glutathione;Mice;Oxidation-Reduction;Glutamate-Cysteine Ligase;Lymphoid Tissue | Document URI: | http://hdl.handle.net/1942/37335 | e-ISSN: | 2041-1723 | DOI: | 10.1038/s41467-022-29426-x | ISI #: | WOS:000778265300019 | Rights: | The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
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