Elucidation of tolerance mechanism against peripheral target antigens in autoimmune diseases

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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.