| First Author | Urbanczyk S | Year | 2022 |
| Journal | Cell Rep | Volume | 39 |
| Issue | 10 | Pages | 110912 |
| PubMed ID | 35675769 | Mgi Jnum | J:326094 |
| Mgi Id | MGI:7294016 | Doi | 10.1016/j.celrep.2022.110912 |
| Citation | Urbanczyk S, et al. (2022) Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle. Cell Rep 39(10):110912 |
| abstractText | 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 HIF1alpha is stabilized. Hence, mitochondrial DNA controls the metabolism of activated B cells via OxPhos to foster humoral immunity. |
