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Article Dans Une Revue Cell Reports Année : 2022

Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle

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Susanne Brodesser

Résumé

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.
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Dates et versions

hal-03692995 , version 1 (15-11-2022)

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Paternité - Pas d'utilisation commerciale - Pas de modification - CC BY 4.0

Identifiants

Citer

Sophia Urbanczyk, Olivier Baris, Jörg Hofmann, R. Verena Taudte, Naïg Guegen, et al.. Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle. Cell Reports, 2022, 39 (10), pp.110912. ⟨10.1016/j.celrep.2022.110912⟩. ⟨hal-03692995⟩
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