Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA.
Lupus. 2013 Apr;22(4):342-9. doi: 10.1177/0961203312471576.
B cells are critical players in the orchestration of properly regulated immune responses, normally providing protective immunity without autoimmunity. Balance in the B cell compartment is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to modulate other components of the innate and adaptive immune system. Autoantibody-independent B cell functions include antigen presentation, T cell activation and polarization, and dendritic cell modulation. Several of these functions are mediated by the ability of B cells to produce immunoregulatory cytokines and chemokines and by their critical contribution to lymphoid tissue development and organization including the development of ectopic tertiary lymphoid tissue. Additionally, the functional versatility of B cells enables them to play either protective or pathogenic roles in autoimmunity. In turn, B cell dysfunction has been critically implicated in the pathophysiology of systemic lupus erythematosus (SLE), a complex disease characterized by the production of autoantibodies and heterogeneous clinical involvement. Thus, the breakdown of B cell tolerance is 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. Once tolerance is broken, 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 IFNα, TNF and IL-1. The complexity of B cell functions has been highlighted by the variable success of B cell-targeted therapies in multiple autoimmune diseases, including those conventionally viewed as T cell-mediated conditions. Given the widespread utilization of B cell depletion therapy in autoimmune diseases and the need for new therapeutic approaches in SLE, a better understanding of human B cell subsets and the balance of pathogenic and regulatory functions is of the essence.
B 细胞是调节适当免疫反应的关键参与者，通常提供保护性免疫而不引起自身免疫。B 细胞池的平衡是通过具有不同抗体依赖性和非依赖性功能的多种 B 细胞群体的精细调节参与来实现的。这两种类型的功能都允许 B 细胞调节先天和适应性免疫系统的其他成分。非自身抗体依赖的 B 细胞功能包括抗原呈递、T 细胞激活和极化以及树突状细胞调节。这些功能中的几种是由 B 细胞产生免疫调节细胞因子和趋化因子的能力以及它们对包括异位三级淋巴组织发育和组织的淋巴组织发育和组织的关键贡献介导的。此外，B 细胞的功能多样性使它们能够在自身免疫中发挥保护或致病作用。反过来，B 细胞功能障碍在系统性红斑狼疮（SLE）的病理生理学中受到了严格的牵连，SLE 是一种复杂的疾病，其特征是产生自身抗体和异质的临床受累。因此，B 细胞耐受的破坏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。一旦耐受被打破，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性细胞因子，包括 IFNα、TNF 和 IL-1。B 细胞功能的复杂性已经通过多种自身免疫性疾病中 B 细胞靶向治疗的可变成功率得到了强调，包括那些传统上被视为 T 细胞介导的疾病。鉴于 B 细胞耗竭疗法在自身免疫性疾病中的广泛应用以及 SLE 中对新治疗方法的需求，更好地了解人类 B 细胞亚群和致病性与调节功能的平衡至关重要。
