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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Muri J,Thut H,Heer S,Krueger CC,Bornkamm GW,Bachmann MF,Kopf Mdoi
10.1002/eji.201848044subject
Has Abstractpub_date
2019-05-01 00:00:00pages
709-723issue
5eissn
0014-2980issn
1521-4141journal_volume
49pub_type
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