Increasing evidence indicates the involvement of B cells in the pathogenesis of multiple sclerosis (MS), but their precise roles are unclear. In this Review, we provide an overview of the development and physiological functions of B cells and the main mechanisms through which B cells are thought to contribute to CNS autoimmunity. In MS, abnormalities of B cell function include pro-inflammatory cytokine production, defective B cell regulatory function and the formation of tertiary lymphoid-like structures in the CNS, which are the likely source of abnormal immunoglobulin production detectable in the cerebrospinal fluid. We also consider the hypothesis that Epstein–Barr virus (EBV) is involved in the B cell overactivation that leads to inflammatory injury to the CNS in MS. We also review the immunological effects — with a focus on the effects on B cell subsets — of several successful therapeutic approaches in MS, including agents that selectively deplete B cells (rituximab, ocrelizumab and ofatumumab), agents that less specifically deplete lymphocytes (alemtuzumab and cladribine) and autologous haematopoietic stem cell transplantation, in which the immune system is unselectively ablated and reconstituted. We consider the insights that these effects on B cell populations provide and their potential to further our understanding and targeting of B cells in MS.

越来越多的证据表明 B 细胞参与了多发性硬化症 (MS) 的发病机制，但它们的确切作用尚不清楚。在这篇综述中，我们概述了 B 细胞的发育和生理功能，以及 B 细胞被认为有助于中枢神经系统自身免疫的主要机制。在 MS 中，B 细胞功能异常包括促炎细胞因子的产生、B 细胞调节功能缺陷和 CNS 中三级淋巴样结构的形成，这些可能是脑脊液中可检测到的异常免疫球蛋白产生的来源。我们还考虑了 Epstein-Barr 病毒 (EBV) 参与导致 MS 中 CNS 炎症损伤的 B 细胞过度激活的假设。我们还回顾了 MS 中几种成功治疗方法的免疫学效应——重点是对 B 细胞亚群的影响，包括选择性耗竭 B 细胞的药物（利妥昔单抗、ocrelizumab 和奥法木单抗）、不太特异性耗尽淋巴细胞的药物（阿仑单抗和克拉屈滨）和自体造血干细胞移植，其中免疫系统被非选择性地消融和重建。我们考虑了这些对 B 细胞群的影响所提供的见解及其潜力，以加深我们对 MS 中 B 细胞的理解和靶向。不太特异性地消耗淋巴细胞的药物（阿仑单抗和克拉屈滨）和自体造血干细胞移植，其中免疫系统被非选择性地消融和重建。我们考虑了这些对 B 细胞群的影响所提供的见解及其潜力，以加深我们对 MS 中 B 细胞的理解和靶向。不太特异性地消耗淋巴细胞的药物（阿仑单抗和克拉屈滨）和自体造血干细胞移植，其中免疫系统被非选择性地消融和重建。我们考虑了这些对 B 细胞群的影响所提供的见解及其潜力，以加深我们对 MS 中 B 细胞的理解和靶向。