The thioredoxin‐1 and glutathione/glutaredoxin‐1 systems redundantly fuel murine B‐cell development and responses. Issue 5 (1st March 2019)

• Record Type: Journal Article
• Authors: Muri, Jonathan; Thut, Helen; Heer, Sebastian; Krueger, Caroline C.; Bornkamm, Georg W.; Bachmann, Martin F.; Kopf, Manfred
• Is Part Of: European journal of immunology. Volume 49:Issue 5(2019)
• Page Start: 709
• Page End: 723
• Publication Date: 2019-03-01
• Subjects: Antibody responses -- B cell development -- Glutaredoxin‐1 -- Thioredoxin‐1; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201848044
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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. Abstract : T cells, MZ B cells, and B1 cells are strictly dependent on the thioredoxin system for DNA biosynthesis and proliferation, while B2 cells with defective thioredoxin system have a backup in the glutaredoxin‐1 system for development and responses. This finding may have implications for therapies of B/T‐cell neoplasms