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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
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
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2019
Prepublished im Jahr
HGF-Berichtsjahr
2019
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 29,
Heft: 9,
Seiten: 2731-2744.e4
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Cell Press
Verlagsort
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Tag d. mündl. Prüfung
0000-00-00
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Gutachter
Prüfer
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Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
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Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er)
Immune Response and Infection
PSP-Element(e)
G-501490-001
Förderungen
Copyright
Erfassungsdatum
2019-12-04