Yoshizaki Ayumi
Department of Dermatology, The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
J Dermatol. 2016 Jan;43(1):39-45. doi: 10.1111/1346-8138.13184.
Systemic sclerosis (SSc) is a connective tissue disease characterized by excessive extracellular matrix deposition in the skin and visceral organs with an autoimmune background. Although the pathogenic relationship between systemic autoimmunity and the clinical manifestations remains unknown, SSc patients have immunological abnormalities including the production of disease-specific autoantibodies. Recent studies have demonstrated that B cells play a crucial role in systemic autoimmunity and disease expression via various functions in addition to autoantibody production. Recent studies show that B cells from SSc patients demonstrate an upregulated CD19 signaling pathway, which is a crucial regulator of B-cell activation, that induces SSc-specific autoantibody production in SSc. In addition, B cells from SSc patients exhibit an overexpression of CD19. Consistently, in CD19 transgenic mice, CD19 overexpression induces SSc-specific autoantibody production. SSc patients have also intrinsic B-cell abnormalities characterized by chronic hyperreactivity of memory B cells, possibly due to CD19 overexpression. Similarly, B cells from a tight-skin mouse, a genetic model of SSc, show augmented CD19 signaling and chronic hyperreactivity. Furthermore, in bleomycin-induced SSc model mice, endogenous ligands for Toll-like receptors, induced by bleomycin treatment, stimulate B cells to produce various fibrogenic cytokines and autoantibodies. Remarkably, CD19 loss results in inhibition of B-cell hyperreactivity and elimination of autoantibody production, which is associated with improvement of fibrosis. Taken together, altered B-cell function may result in tissue fibrosis, as well as autoimmunity, in SSc. Although further studies and greater understanding are needed, B cells are potential therapeutic target in SSc.
系统性硬化症（SSc）是一种结缔组织疾病，其特征为在自身免疫背景下，皮肤和内脏器官中细胞外基质过度沉积。尽管全身自身免疫与临床表现之间的致病关系尚不清楚，但SSc患者存在免疫异常，包括产生疾病特异性自身抗体。最近的研究表明，B细胞除了产生自身抗体外，还通过多种功能在全身自身免疫和疾病表达中发挥关键作用。最近的研究表明，SSc患者的B细胞显示CD19信号通路上调，而CD19信号通路是B细胞活化的关键调节因子，可诱导SSc中SSc特异性自身抗体的产生。此外，SSc患者的B细胞表现出CD19的过表达。同样，在CD19转基因小鼠中，CD19过表达诱导SSc特异性自身抗体的产生。SSc患者还存在内在的B细胞异常，其特征为记忆B细胞的慢性高反应性，这可能是由于CD19过表达所致。类似地，来自紧皮小鼠（SSc的一种遗传模型）的B细胞显示CD19信号增强和慢性高反应性。此外，在博来霉素诱导的SSc模型小鼠中，博来霉素治疗诱导的Toll样受体内源性配体刺激B细胞产生各种促纤维化细胞因子和自身抗体。值得注意的是，CD19缺失导致B细胞高反应性受到抑制，自身抗体产生被消除，这与纤维化的改善相关。综上所述，B细胞功能改变可能导致SSc中的组织纤维化以及自身免疫。尽管还需要进一步研究和深入了解，但B细胞是SSc潜在的治疗靶点。
