PMID- 35675769
OWN - NLM
STAT- MEDLINE
DCOM- 20220610
LR  - 20220912
IS  - 2211-1247 (Electronic)
VI  - 39
IP  - 10
DP  - 2022 Jun 7
TI  - Mitochondrial respiration in B lymphocytes is essential for humoral immunity by 
      controlling the flux of the TCA cycle.
PG  - 110912
LID - S2211-1247(22)00689-1 [pii]
LID - 10.1016/j.celrep.2022.110912 [doi]
AB  - 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.
CI  - Copyright (c) 2022 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Urbanczyk, Sophia
AU  - Urbanczyk S
AD  - Division of Molecular Immunology, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Baris, Olivier R
AU  - Baris OR
AD  - MitoVasc, University of Angers, UMR CNRS 6015/INSERM U1083, Angers, France.
FAU - Hofmann, Jorg
AU  - Hofmann J
AD  - Chair of Biochemistry, Department Biology, FAU Erlangen-Nurnberg, Erlangen, 
      Germany.
FAU - Taudte, R Verena
AU  - Taudte RV
AD  - Institute of Experimental and Clinical Pharmacology and Toxicology, 
      Universitatsklinikum Erlangen, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Guegen, Naig
AU  - Guegen N
AD  - MitoVasc, University of Angers, UMR CNRS 6015/INSERM U1083, Angers, France; 
      Department of Biochemistry and Genetics, University Hospital, Angers, France.
FAU - Golombek, Florian
AU  - Golombek F
AD  - Chair of Bioprocess Engineering, Technical Faculty, FAU Erlangen-Nurnberg, 
      Erlangen, Germany.
FAU - Castiglione, Kathrin
AU  - Castiglione K
AD  - Chair of Bioprocess Engineering, Technical Faculty, FAU Erlangen-Nurnberg, 
      Erlangen, Germany.
FAU - Meng, Xianyi
AU  - Meng X
AD  - Deparment of Internal Medicine III, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Bozec, Aline
AU  - Bozec A
AD  - Deparment of Internal Medicine III, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Thomas, Jana
AU  - Thomas J
AD  - Division of Molecular Immunology, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Weckwerth, Leonie
AU  - Weckwerth L
AD  - Division of Molecular Immunology, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Mougiakakos, Dimitrios
AU  - Mougiakakos D
AD  - Deparment of Internal Medicine V, Universitatsklinikum Erlangen, Translational 
      Research Center, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Schulz, Sebastian R
AU  - Schulz SR
AD  - Division of Molecular Immunology, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Schuh, Wolfgang
AU  - Schuh W
AD  - Division of Molecular Immunology, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Schlotzer-Schrehardt, Ursula
AU  - Schlotzer-Schrehardt U
AD  - Department Kopfklinik, Division of Ophthalmology, FAU Erlangen-Nurnberg, 
      Erlangen, Germany.
FAU - Steinmetz, Tobit D
AU  - Steinmetz TD
AD  - Division of Molecular Immunology, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany.
FAU - Brodesser, Susanne
AU  - Brodesser S
AD  - University of Cologne, Faculty of Medicine and University Hospital of Cologne, 
      Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases 
      (CECAD), Cologne, Germany.
FAU - Wiesner, Rudolf J
AU  - Wiesner RJ
AD  - University of Cologne, Faculty of Medicine and University Hospital of Cologne, 
      Cluster of Excellence Cellular Stress Responses in Aging-associated Diseases 
      (CECAD), Cologne, Germany; Center for Physiology and Pathophysiology, Institute 
      of Vegetative Physiology and Center for Molecular Medicine Cologne (CMMC), 
      University of Cologne, Cologne, Germany.
FAU - Mielenz, Dirk
AU  - Mielenz D
AD  - Division of Molecular Immunology, Universitatsklinikum Erlangen, 
      Nikolaus-Fiebiger-Zentrum, FAU Erlangen-Nurnberg, Erlangen, Germany. Electronic 
      address: dirk.mielenz@fau.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes
MH  - *Citric Acid Cycle
MH  - DNA, Mitochondrial/metabolism
MH  - Glycolysis/genetics
MH  - *Immunity, Humoral
MH  - Lipopolysaccharides/metabolism
MH  - Mice
MH  - Respiration
OTO - NOTNLM
OT  - B lymphocyte
OT  - CP: Immunology
OT  - HIF1
OT  - TCA cycle
OT  - class switch recombination
OT  - germinal center
OT  - hypoxia inducible factor 1
OT  - mTOR
OT  - mammalian target of Rapamycin
OT  - mitochondrial DNA
OT  - mitochondrial respiration
OT  - oxidative phosphorylation
OT  - phosphatidic acid
OT  - plasma cell
COIS- Declaration of interests The authors declare no competing interests.
EDAT- 2022/06/09 06:00
MHDA- 2022/06/11 06:00
CRDT- 2022/06/08 18:22
PHST- 2021/05/03 00:00 [received]
PHST- 2021/12/28 00:00 [revised]
PHST- 2022/05/12 00:00 [accepted]
PHST- 2022/06/08 18:22 [entrez]
PHST- 2022/06/09 06:00 [pubmed]
PHST- 2022/06/11 06:00 [medline]
AID - S2211-1247(22)00689-1 [pii]
AID - 10.1016/j.celrep.2022.110912 [doi]
PST - ppublish
SO  - Cell Rep. 2022 Jun 7;39(10):110912. doi: 10.1016/j.celrep.2022.110912.