Elucidation of tolerance mechanism against peripheral target antigens in autoimmune diseases

本研究的目的是以抗桥粒蛋白3自身抗体(Dsg3)为模型疾病，探讨寻常型天疱疮的外周耐受机制。Dsg3特异性T细胞在产生抗Dsg3抗体的过程中表现出致病异质性，而IL-4是这一过程中的关键细胞因子。单个辅助性T细胞克隆足以诱导多克隆幼稚B细胞产生致病抗体。致病免疫球蛋白诱导组织损伤时，成熟的Dsg3特异性B细胞通过Fas介导的过程以依赖于T细胞的方式被清除，提示了一种新的外周B细胞耐受机制。

The purpose of this study is to clarify the mechanisms of peripheral tolerance using pemphigus vulgaris which is mediated by IgG autoantibodies against desmoglein 3 (Dsg3) as a model disease. Dsg3-specific T cells showed pathogenic heterogeneity in anti-Dsg3 IgG production and IL-4 was a key cytokine in this process. A single helper T cell clone was sufficient to commit polyclonal naive B cells to produce pathogenic IgG. Mature Dsg3-specific B cells were eliminated via a Fas-mediated process in a CD4^+ T cell dependent fashion when tissue damages were induced by pathogenic IgG, suggesting a novel peripheral B cell tolerance mechanism.