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B1 and marginal zone B cells but not follicular B2 cells require Gpx4 to prevent lipid peroxidation and ferroptosis.
Cell Rep. 29, 2731-2744.e4 (2019)
Aerobic organisms need to maintain cellular redox homeostasis. Glutathione peroxidase-4 (Gpx4) has the unique ability to protect cells against lipid peroxidation. Here, we show that Gpx4 is absolutely required to prevent ferroptosis during development, maintenance, and responses of innate-like B cells, namely, the B1 and marginal zone (MZ) B cells. In contrast, Gpx4 is dispensable for the development, germinal center reactions, and antibody responses of follicular B2 cells. Mechanistically, we show increased lipid metabolism and sensitivity to lipid peroxidation and ferroptosis in B1 and MZ B cells compared to follicular B2 cells, consistent with the requirement of Gpx4 in innate-like B cells. This high sensitivity to ferroptosis of innate-like B cells may be used to therapeutically target Gpx4 in certain forms of B cell malignancies involving B1 cells.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
B Cell Immunometabolism ; B1 Cells ; Fatty-acid Metabolism ; Ferroptosis ; Glutathione ; Gpx4 ; Lipid Ros ; Marginal Zone B Cells ; Redox System; Hydroperoxide Glutathione-peroxidase; Oxidative Stress; Metabolism; Regulator; Dna; Differentiation; Homeostasis; Biology; Damage; Ros
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 29,
Issue: 9,
Pages: 2731-2744.e4
Publisher
Cell Press
Publishing Place
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Non-patent literature
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Reviewing status
Peer reviewed