Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle
| Autor: | Sophia Urbanczyk, Olivier R. Baris, Jörg Hofmann, R. Verena Taudte, Naïg Guegen, Florian Golombek, Kathrin Castiglione, Xianyi Meng, Aline Bozec, Jana Thomas, Leonie Weckwerth, Dimitrios Mougiakakos, Sebastian R. Schulz, Wolfgang Schuh, Ursula Schlötzer-Schrehardt, Tobit D. Steinmetz, Susanne Brodesser, Rudolf J. Wiesner, Dirk Mielenz |
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| Přispěvatelé: | Universitätsklinikum Erlangen [Erlangen], MitoVasc - Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), University of Cologne, Baris, Olivier |
| Rok vydání: | 2022 |
| Předmět: |
Lipopolysaccharides
plasma cell [SDV]Life Sciences [q-bio] HIF1 Citric Acid Cycle oxidative phosphorylation mitochondrial DNA DNA Mitochondrial General Biochemistry Genetics and Molecular Biology Mice mitochondrial respiration Animals ddc:610 TCA cycle B-Lymphocytes B lymphocyte Respiration Immunity Humoral [SDV] Life Sciences [q-bio] mammalian target of Rapamycin phosphatidic acid germinal center mTOR hypoxia inducible factor 1 class switch recombination Glycolysis |
| Zdroj: | Cell Reports Cell Reports, 2022, 39 (10), pp.110912. ⟨10.1016/j.celrep.2022.110912⟩ |
| ISSN: | 2211-1247 |
| Popis: | International audience; To elucidate the function of oxidative phosphorylation (OxPhos) during B cell differentiation, we employ CD23Cre-driven expression of the dominant-negative K320E mutant of the mitochondrial helicase Twinkle (DNT). DNT-expression depletes mitochondrial DNA during B cell maturation, reduces the abundance of respiratory chain protein subunits encoded by mitochondrial DNA, and, consequently, respiratory chain super-complexes in activated B cells. Whereas B cell development in DNT mice is normal, B cell proliferation, germinal centers, class switch to IgG, plasma cell maturation, and T cell-dependent as well as T cell-independent humoral immunity are diminished. DNT expression dampens OxPhos but increases glycolysis in lipopolysaccharide and B cell receptor-activated cells. Lipopolysaccharide-activated DNT-B cells exhibit altered metabolites of glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle and a lower amount of phosphatidic acid. Consequently, mTORC1 activity and BLIMP1 induction are curtailed, whereas HIF1α is stabilized. Hence, mitochondrial DNA controls the metabolism of activated B cells via OxPhos to foster humoral immunity. |
| Databáze: | OpenAIRE |
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