Urbanczyk, Sophia, Baris, Olivier R., Hofmann, Joerg ORCID: 0000-0001-7387-1569, Taudte, R. Verena, Guegen, Naig, Golombek, Florian, Castiglione, Kathrin, Meng, Xianyi, Bozec, Aline, Thomas, Jana, Weckwerth, Leonie, Mougiakakos, Dimitrios, Schulz, Sebastian R., Schuh, Wolfgang, Schloetzer-Schrehardt, Ursula, Steinmetz, Tobit D., Brodesser, Susanne, Wiesner, Rudolf J. and Mielenz, Dirk (2022). Mitochondrial respiration in B lymphocytes is essential for humoral immunity by controlling the flux of the TCA cycle. Cell Reports, 39 (10). CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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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 HIF1a is stabilized. Hence, mitochondrial DNA controls the metabolism of activated B cells via OxPhos to foster humoral immunity.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Urbanczyk, SophiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Baris, Olivier R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hofmann, JoergUNSPECIFIEDorcid.org/0000-0001-7387-1569UNSPECIFIED
Taudte, R. VerenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guegen, NaigUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Golombek, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castiglione, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meng, XianyiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bozec, AlineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, JanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weckwerth, LeonieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mougiakakos, DimitriosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulz, Sebastian R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schuh, WolfgangUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schloetzer-Schrehardt, UrsulaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steinmetz, Tobit D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brodesser, SusanneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesner, Rudolf J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mielenz, DirkUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-682161
DOI: 10.1016/j.celrep.2022.110912
Journal or Publication Title: Cell Reports
Volume: 39
Number: 10
Date: 2022
Publisher: CELL PRESS
Place of Publication: CAMBRIDGE
ISSN: 2211-1247
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PLASMA-CELL DIFFERENTIATION; PHOSPHATIDIC-ACID; CHAIN COMPLEXES; MTOR; TRANSCRIPTION; METABOLISM; ACTIVATION; RECEPTOR; METABOLOMICS; MAINTENANCEMultiple languages
Cell BiologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/68216

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