Laboratory of immune regulation, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
Immunol Rev. 2010 Jan;233(1):146-61. doi: 10.1111/j.0105-2896.2009.00855.x.
B lymphocytes contribute to immunity through production of antibodies, antigen presentation to T cells, and secretion of cytokines. B cells are generally considered in autoimmune diseases as drivers of pathogenesis. This view is certainly justified, given the successful utilization of the B cell-depleting reagent rituximab in patients with rheumatoid arthritis or other autoimmune pathologies. In a number of cases, however, the depletion of B cells led to an exacerbation of symptoms in patients with autoimmune disorders. In a similar manner, mice lacking B cells can develop an aggravated course of disease in several autoimmune models. These paradoxical observations are now explained by the concept that activated B cells can suppress immune responses through the production of cytokines, especially interleukin-10. Here, we review the stimulatory signals that induce interleukin-10 secretion and suppressive functions in B cells and the phenotype of the B cells with such characteristics. Finally, we formulate a model explaining how this process of immune regulation by activated B cells can confer advantageous properties to the immune system in its combat with pathogens. Altogether, this review proposes that B-cell-mediated regulation is a fundamental property of the immune system, with features of great interest for the development of new cell-based therapies for autoimmune diseases.
B 细胞通过产生抗体、向 T 细胞呈递抗原和分泌细胞因子来促进免疫。在自身免疫性疾病中，B 细胞通常被认为是发病机制的驱动因素。鉴于 B 细胞耗竭试剂利妥昔单抗在类风湿关节炎或其他自身免疫性疾病患者中的成功应用，这种观点无疑是合理的。然而，在许多情况下，B 细胞的耗竭导致自身免疫性疾病患者的症状恶化。类似地，缺乏 B 细胞的小鼠在几种自身免疫模型中会发展出病情加重的过程。这些矛盾的观察结果现在可以用这样的概念来解释，即激活的 B 细胞可以通过产生细胞因子，特别是白细胞介素-10，来抑制免疫反应。在这里，我们综述了诱导 B 细胞产生白细胞介素-10 分泌和抑制功能的刺激信号，以及具有这种特征的 B 细胞表型。最后，我们提出了一个模型，解释了激活的 B 细胞如何通过这种免疫调节过程在与病原体的斗争中赋予免疫系统有利的特性。总之，这篇综述提出 B 细胞介导的调节是免疫系统的一个基本特性，对于开发治疗自身免疫性疾病的新型基于细胞的疗法具有重要意义。
