Ding Chuanlin, Yan Jun
Tumor Immunobiology Program, Department of Medicine, James Graham Brown Cancer Center, Delia D. Baxter Research Building, Room 119A, University of Louisville, 580 South Preston Street, Louisville, KY 40202, USA.
Arch Immunol Ther Exp (Warsz). 2007 Mar-Apr;55(2):83-9. doi: 10.1007/s00005-007-0011-0. Epub 2007 Mar 9.
It has become clear that the autoreactive B cells are a part of the normal naïve B cell repertoire in the periphery, despite the fact that they undergo a series of checkpoints, which include receptor editing (revision), clonal deletion, and anergy. However, most of those B cells reactive against self antigen remain functionally naïve for autoantibody production by differential peripheral checkpoints. Therefore, the presence of autoreactive B cells does not always signify disease. Regulation of their activation and effector functions will determine the ultimate outcome. Although autoreactive B cell tolerance is well maintained in the healthy individual, the existence of pathogenic autoantibodies in autoimmune diseases indicates that these tolerogenic checkpoints are broken. Recent studies have demonstrated that autoreactive B cells are regulated by a composite of factors, such as genetic susceptibility and environmental triggers such as bacterial and viral infections as well as other immune cells. Interestingly, Toll-like receptors, previously considered as pattern-recognition receptors to detect and sense pathogens, may also have a potential to recognize self antigens and regulate autoreactive B cells for activation. Understanding the mechanisms of autoreactive B cell regulation and activation may help in identifying novel targets for the treatment of autoimmune diseases.
已经清楚的是，自身反应性B细胞是外周正常幼稚B细胞库的一部分，尽管它们会经历一系列检查点，包括受体编辑（修正）、克隆清除和失能。然而，大多数针对自身抗原的B细胞通过不同的外周检查点在功能上仍保持幼稚，无法产生自身抗体。因此，自身反应性B细胞的存在并不总是意味着疾病。对其激活和效应功能的调节将决定最终结果。虽然在健康个体中自身反应性B细胞的耐受性得到很好的维持，但自身免疫性疾病中致病性自身抗体的存在表明这些耐受性检查点被打破。最近的研究表明，自身反应性B细胞受到多种因素的综合调节，如遗传易感性以及细菌和病毒感染等环境触发因素以及其他免疫细胞。有趣的是，Toll样受体以前被认为是检测和感知病原体的模式识别受体，现在也可能有识别自身抗原并调节自身反应性B细胞激活的潜力。了解自身反应性B细胞调节和激活的机制可能有助于确定治疗自身免疫性疾病的新靶点。
