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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)
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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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Publication type Article: Journal article
Document type Scientific Article
Keywords Antibody Responses ; B Cell Development ; Glutaredoxin-1 ; Thioredoxin-1; Marginal Zone; Glutathione; Reductase; Metabolism; Differentiation; Inhibition; Apoptosis; Pathways; Embryogenesis; Recombination
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Quellenangaben Volume: 49, Issue: 5, Pages: 709-723 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed