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

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. While B-cell development in DNT-mice is normal, B-cell proliferation, germinal centers and class switch to IgG, plasma cell maturation, 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 while HIF1a is stabilized. Hence, mtDNA controls the metabolism of activated B-cells via OxPhos to foster humoral immunity.

INSTRUMENT(S): Liquid Chromatography MS -

PROVIDER: MTBLS4647 | MetaboLights | 2026-08-21

REPOSITORIES: MetaboLights