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

Urbanczyk S, Baris OR, Hofmann J, Taudte V, Guegen N, Golombek F, Castiglione K, Meng X, Bozec A, Thomas J, Weckwerth L, Mougiakakos D, Schulz S, Schuh W, Schlötzer-Schrehardt U, Steinmetz T, Brodesser S, Wiesner RJ, Mielenz D (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 39

Pages Range: 110912-

Journal Issue: 10

DOI: 10.1016/j.celrep.2022.110912

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.

Authors with CRIS profile

Sophia Urbanczyk Department of Molecular Immunology Jörg Hofmann Lehrstuhl für Biochemie Verena Taudte Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie Florian Golombek Lehrstuhl für Bioverfahrenstechnik Kathrin Castiglione Lehrstuhl für Bioverfahrenstechnik Xianyi Meng Juniorprofessur für Osteoimmunologie Aline Bozec Juniorprofessur für Osteoimmunologie Jana Thomas Department of Molecular Immunology Leonie Weckwerth Department of Molecular Immunology Dimitrios Mougiakakos Medizinische Fakultät Sebastian Schulz Professur für Immunologie Wolfgang Schuh Department of Molecular Immunology Ursula Schlötzer-Schrehardt Medizinische Fakultät Tobit Steinmetz Professur für Immunologie Dirk Mielenz Medizinische Fakultät

Involved external institutions

Universitätsklinikum Köln DE Germany (DE) Université d'Angers FR France (FR)

How to cite

APA:

Urbanczyk, S., Baris, O.R., Hofmann, J., Taudte, V., Guegen, N., Golombek, F.,... Mielenz, D. (2022). Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle. Cell Reports, 39(10), 110912-. https://dx.doi.org/10.1016/j.celrep.2022.110912

MLA:

Urbanczyk, Sophia, et al. "Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle." Cell Reports 39.10 (2022): 110912-.

BibTeX: Download