Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Precision Institute of Immunology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Curr Opin Pharmacol. 2020 Dec;55:90-98. doi: 10.1016/j.coph.2020.10.002. Epub 2020 Nov 6.
B cells are critical to immune homeostasis at mucosal surfaces including those of the gastrointestinal tract. B cell-related abnormalities, comprising of a lympho-plasmacytic infiltrate, as well as anti-microbial antibodies, are well reported in patients with inflammatory bowel disease (IBD). However, B cell-targeting is not part of the therapeutic armamentarium in IBD. Recently, driven by the identification of genetic associations between IgG Fc receptors and IBD susceptibility, there has been renewed interest in defining the immunobiology of B cells during mucosal inflammation. Functional studies have demonstrated mechanisms of IgG-mediated disease pathogenesis and deep mucosal immunophenotyping using single cell RNA sequencing has elaborated a significant remodelling of the B cell compartment in IBD. In light of these novel data, here we discuss potential strategies to target B cell immunity in IBD. Finally, we discuss potential risks and pitfalls of these approaches and emphasize on distinguishing between homeostatic and pathological B cell signatures, allowing for a data-based, prudent therapeutic approach.
B 细胞对于包括胃肠道在内的黏膜表面的免疫稳态至关重要。在炎症性肠病 (IBD) 患者中，已报道了与 B 细胞相关的异常，包括淋巴浆细胞浸润和抗微生物抗体。然而，B 细胞靶向治疗并不是 IBD 治疗手段的一部分。最近，由于 IgG Fc 受体与 IBD 易感性之间的遗传关联的确定，人们重新关注黏膜炎症期间 B 细胞的免疫生物学。功能研究已经证明了 IgG 介导的疾病发病机制的机制，并且使用单细胞 RNA 测序进行的深度黏膜免疫表型分析详细阐述了 IBD 中 B 细胞区室的显著重塑。鉴于这些新数据，我们在这里讨论了在 IBD 中靶向 B 细胞免疫的潜在策略。最后，我们讨论了这些方法的潜在风险和陷阱，并强调区分稳态和病理性 B 细胞特征，允许基于数据的谨慎治疗方法。
