Dysfunction of CD19(+)CD24(hi)CD27(+) B regulatory cells in patients with bullous pemphigoid

Bullous pemphigoid (BP) is an autoimmune blistering skin disease characterized by the production of autoantibodies against the hemidesmosomal protein BP180. B regulatory cells (Bregs) are crucial in maintaining self-tolerance and suppressing autoantibody production. However, it is still unclear whether the dysfunctions of Bregs contributes to the autoantibody production in BP patients. In this study, we found that CD19(+)CD24(hi)CD27(+) Bregs and IL-10(+)CD19(+) Bregs were significantly increased in the peripheral blood samples of BP patients compared with that in healthy controls. Moreover, compared to Bregs from healthy individuals, we found that Bregs from BP patients fails to suppress the production of specific anti-BP180 autoantibody when co-cultured with patient-derived PBMCs. Additionally, Bregs from BP patients were defective in suppressing the CD4(+) T cell proliferation and the cytokines expression (including IFN-γ, TNF-α and IL-4). Notably, we found that patient-derived Bregs produced high level of TNF-α and the TNF inhibitor etanercept could inhibit the autoantibody production in the culture system in vitro. Our results indicate that Bregs from BP patient appear phenotypically pro-inflammatory by their cytokine profile and are defective in immunosuppressive function, which suggest that Bregs play a pro-inflammatory role rather than a regulatory role in the pathogenesis of BP.