Autoimmune diseases with B cell–directed therapeutics approved by the US Food and Drug Administration are surprisingly diverse in clinical manifestations and pathophysiology. In this review, we focus on recent clinical and mechanistic insights into the efficacy of B cell depletion in these diverse autoimmune disorders, the rapidly expanding armamentarium of approved agents, and future approaches. The pathogenic roles for B cells include direct functions such as production of autoantibodies and proinflammatory cytokines and indirect functions via antigen presentation to T cells. The efficacy of B cell–depleting strategies varies across diseases and likely reflects the complexity of disease pathogenesis and relative contribution of B cell roles. Additionally, B cell–depleting therapies do not equally target all B cell subsets in all patients, and this likely explains some of the variability in responses. Recent reports of B cell depletion with novel chimeric antigen receptor (CAR) T cell approaches in an expanding number of autoimmune diseases highlight the potential role of B cell depletion in resetting immune tolerance. The relative importance of eliminating autoreactive B cells and plasma cells and approaches to doing so will also be discussed.

中文翻译：

---

B 细胞定向治疗自身免疫性疾病


美国食品和药物管理局批准的 B 细胞定向治疗的自身免疫性疾病在临床表现和病理生理学方面具有惊人的多样性。在这篇综述中，我们重点关注 B 细胞耗竭在这些不同自身免疫性疾病中的功效的最新临床和机制见解、快速扩大的已批准药物的武器库以及未来的方法。 B 细胞的致病作用包括直接功能（例如产生自身抗体和促炎细胞因子）和通过抗原呈递给 T 细胞的间接功能。 B 细胞耗竭策略的功效因疾病而异，可能反映了疾病发病机制的复杂性和 B 细胞作用的相对贡献。此外，B 细胞耗竭疗法并未同等针对所有患者的所有 B 细胞亚群，这可能解释了反应的一些变异性。最近关于在越来越多的自身免疫性疾病中使用新型嵌合抗原受体 (CAR) T 细胞方法消除 B 细胞的报道强调了 B 细胞消除在重置免疫耐受中的潜在作用。还将讨论消除自身反应性 B 细胞和浆细胞的相对重要性以及实现这一目标的方法。