The Multiple Roles of B Cells in the Pathogenesis of Sjögren's Syndrome.

The Multiple Roles of B Cells in the Pathogenesis of Sjögren's Syndrome.
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DOI:
10.3389/fimmu.2021.684999
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发表时间:
2021
影响因子:
7.3
通讯作者:
Lu L
Lu L
中科院分区:
医学2区
文献类型:
--
作者:
Du W;Han M;Zhu X;Xiao F;Huang E;Che N;Tang X;Zou H;Jiang Q;Lu L

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原发性干燥综合征(pSS)是一种慢性自身免疫性疾病,其特征是淋巴细胞浸润和唾液腺等外分泌腺组织破坏。尽管外分泌腺中异位淋巴组织的形成和自身反应性 B 细胞过度产生自身抗体凸显了 B 细胞在疾病发展中的关键参与,但各种 B 细胞亚群在 pSS 发病机制中的确切作用仍部分了解。目前的研究已经确定了几种在 pSS 中具有多种功能的新型 B 细胞亚群,其中自身反应性年龄相关 B 细胞和自身抗体产生增强的浆细胞有助于疾病进展。此外,促炎细胞因子产生增强的组织驻留型 Fc 受体样 4 (FcRL4)+ B 细胞亚群是患有粘膜相关淋巴组织 (MALT) 淋巴瘤的 pSS 患者的关键驱动因素。最近,发现 pSS 患者中免疫抑制功能受损的调节性 B (Breg) 细胞与滤泡辅助 T (Tfh) 细胞呈负相关。进一步的研究揭示了 Breg 细胞在限制自身免疫发病机制中 Tfh 反应中的关键作用。本综述概述了致病性 B 细胞亚群和 Breg 细胞鉴定的最新进展,以及 pSS 患者 B 细胞靶向治疗的新进展。
Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease characterized by lymphocytic infiltration and tissue destruction of exocrine glands such as salivary glands. Although the formation of ectopic lymphoid tissue in exocrine glands and overproduction of autoantibodies by autoreactive B cells highlight the critical involvement of B cells in disease development, the precise roles of various B cell subsets in pSS pathogenesis remain partially understood. Current studies have identified several novel B cell subsets with multiple functions in pSS, among which autoreactive age-associated B cells, and plasma cells with augmented autoantibody production contribute to the disease progression. In addition, tissue-resident Fc Receptor-Like 4 (FcRL4)+ B cell subset with enhanced pro-inflammatory cytokine production serves as a key driver in pSS patients with mucosa-associated lymphoid tissue (MALT)-lymphomas. Recently, regulatory B (Breg) cells with impaired immunosuppressive functions are found negatively correlated with T follicular helper (Tfh) cells in pSS patients. Further studies have revealed a pivotal role of Breg cells in constraining Tfh response in autoimmune pathogenesis. This review provides an overview of recent advances in the identification of pathogenic B cell subsets and Breg cells, as well as new development of B-cell targeted therapies in pSS patients.
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