Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle.
Cell Rep
; 39(10): 110912, 2022 06 07.
Article
em En
| MEDLINE
| ID: mdl-35675769
ABSTRACT
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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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ciclo do Ácido Cítrico
/
Imunidade Humoral
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article