Division of Allergy Immunology Rheumatology, Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 695, Rochester, NY 14642, USA.
Rheum Dis Clin North Am. 2010 Feb;36(1):109-30, viii-ix. doi: 10.1016/j.rdc.2009.12.002.
Systemic lupus erythematosus (SLE) is a complex disease characterized by numerous autoantibodies and clinical involvement in multiple organ systems. The immunologic events triggering the onset and progression of clinical manifestations have not yet been fully defined, but a central role for B cells in the pathogenesis has been brought to the fore in the last several years. The breakdown of B-cell tolerance is likely a defining and early event in the disease process and may occur by multiple pathways, including alterations in factors that affect B-cell activation thresholds, B-cell longevity, and apoptotic cell processing. Antibody-dependent and -independent mechanisms of B cells are important in SLE. Thus, autoantibodies contribute to autoimmunity by multiple mechanisms including immune complex mediated type III hypersensitivity reactions, type II antibody-dependent cytotoxicity, and by instructing innate immune cells to produce pathogenic cytokines including interferon alpha, tumor necrosis factor, and interleukin 1. Recent data have highlighted the critical role of toll-like receptors as a link between the innate and adaptive immune system in SLE immunopathogenesis. Given the large body of evidence implicating abnormalities in the B-cell compartment in SLE, there has been a therapeutic focus on developing interventions that target the B-cell compartment. Several different approaches to targeting B cells have been used, including B-cell depletion with monoclonal antibodies against B-cell-specific molecules, induction of negative signaling in B cells, and blocking B-cell survival and activation factors. Overall, therapies targeting B cells are beginning to show promise in the treatment of SLE and continue to elucidate the diverse roles of B cells in this complex disease.
系统性红斑狼疮（SLE）是一种复杂的疾病，其特征是存在多种自身抗体，并在多个器官系统中出现临床受累。触发临床症状发生和进展的免疫事件尚未完全确定，但近年来，B 细胞在发病机制中的核心作用已被突显出来。B 细胞耐受的破坏可能是疾病过程中的一个定义性和早期事件，并且可能通过多种途径发生，包括影响 B 细胞激活阈值、B 细胞寿命和凋亡细胞处理的因素的改变。B 细胞的抗体依赖和非依赖机制在 SLE 中很重要。因此，自身抗体通过多种机制导致自身免疫，包括免疫复合物介导的 III 型超敏反应、II 型抗体依赖性细胞毒性，以及指导先天免疫细胞产生致病细胞因子，包括干扰素-α、肿瘤坏死因子和白细胞介素 1。最近的数据强调了 Toll 样受体作为 SLE 免疫发病机制中先天和适应性免疫系统之间联系的关键作用。鉴于大量证据表明 B 细胞区室异常与 SLE 有关，因此一直将治疗重点放在开发针对 B 细胞区室的干预措施上。已经使用了几种针对 B 细胞的不同方法，包括针对 B 细胞特异性分子的单克隆抗体进行 B 细胞耗竭、诱导 B 细胞中的负信号以及阻断 B 细胞存活和激活因子。总体而言，针对 B 细胞的治疗方法开始在 SLE 的治疗中显示出前景，并继续阐明 B 细胞在这种复杂疾病中的多种作用。
