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

Muri, Jonathan; Thut, Helen; Heer, Sebastian; Krüger, Caroline C.; Bornkamm, Georg W; Bachmann, Martin F.; Kopf, Manfred (2019). The thioredoxin-1 and glutathione/glutaredoxin-1 systems redundantly fuel murine B-cell development and responses. European journal of immunology, 49(5), pp. 709-723. Wiley-VCH 10.1002/eji.201848044

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

UniBE Contributor:

Krüger, Caroline Claire and Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0014-2980

Publisher:

Wiley-VCH

Language:

English

Submitter:

Lee-Anne Brand

Date Deposited:

18 Nov 2019 10:35

Last Modified:

01 Mar 2020 02:30

Publisher DOI:

10.1002/eji.201848044

PubMed ID:

30802940

Uncontrolled Keywords:

Antibody responses B cell development Glutaredoxin-1 Thioredoxin-1

BORIS DOI:

10.7892/boris.135093

URI:

https://boris.unibe.ch/id/eprint/135093

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