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Muri, J.* ; Thut, H.* ; Heer, S.* ; Krueger, C.C.* ; Bornkamm, G.W. ; Bachmann, M.F.* ; Kopf, M.*

The thioredoxin-1 and glutathione/glutaredoxin-1 systems redundantly fuel murine B-cell development and responses.

Eur. J. Immunol. 49, 709-723 (2019)
Verlagsversion Postprint Forschungsdaten DOI PMC
Open Access Green
Antioxidant systems maintain cellular redox homeostasis. The thioredoxin-1 (Trx1) and the glutathione (GSH)/glutaredoxin-1 (Grx1) systems are key players in preserving cytosolic redox balance. In fact, T lymphocytes critically rely on reducing equivalents from the Trx1 system for DNA biosynthesis during metabolic reprogramming upon activation. We here show that the Trx1 system is also indispensable for development and functionality of marginal zone (MZ) B cells and B1 cells in mice. In contrast, development of conventional B cells, follicular B-cell homeostasis, germinal center reactions, and antibody responses are redundantly sustained by both antioxidant pathways. Proliferating B2 cells lacking Txnrd1 have increased glutathione (GSH) levels and upregulated cytosolic Grx1, which is barely detectable in expanding thymocytes. These results suggest that the redox capacity driving proliferation is more robust and flexible in B cells than in T cells, which may have profound implications for the therapy of B and T-cell neoplasms.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Antibody Responses ; B Cell Development ; Glutaredoxin-1 ; Thioredoxin-1; Marginal Zone; Glutathione; Reductase; Metabolism; Differentiation; Inhibition; Apoptosis; Pathways; Embryogenesis; Recombination
Sprache englisch
Veröffentlichungsjahr 2019
HGF-Berichtsjahr 2019
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Zeitschrift European Journal of Immunology
Quellenangaben Band: 49, Heft: 5, Seiten: 709-723 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Hoboken
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Clinical Molecular Biology and Tumor Genetics (K.MOLBI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501490-001
DOI 10.1002/eji.201848044
WOS ID WOS:000465252500007
Scopus ID 85062337883
PubMed ID 30802940
Erfassungsdatum 2019-03-01
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