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

Davide G. Franchina, Henry Kurniawan, Melanie Grusdat, Carole Binsfeld, Luana Guerra, Lynn Bonetti, Leticia Soriano-Baguet, Anouk Ewen, Takumi Kobayashi, Sophie Farinelle, Anna Rita Minafra, Niels Vandamme, Anaïs Carpentier, Felix K. Borgmann, Christian Jäger, Ying Chen, Markus Kleinewietfeld, Vasilis Vasiliou, Michel Mittelbronn, Karsten HillerPhilipp A. Lang, Dirk Brenner*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Article number1789
Pages (from-to)1789
JournalNature Communications
Volume13
Issue number1
DOIs
Publication statusPublished - 4 Apr 2022

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