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.

有氧生物需要维持细胞氧化还原稳态。谷胱甘肽过氧化物酶4（Gpx4）具有保护细胞抵抗脂质过氧化的独特能力。在这里，我们显示Gpx4是绝对必需的，以防止在发育，维持和先天性B细胞（即B1和边缘区（MZ）B细胞）反应期间发生肥大症。相反，Gpx4对于卵泡B2细胞的发育，生发中心反应和抗体反应是必不可少的。从机理上讲，与卵泡B2细胞相比，我们发现B1和MZ B细胞的脂质代谢增加，并且对脂质过氧化和肥大症的敏感性增强，这与先天性B细胞中Gpx4的需求一致。