Defective Regulatory B Cells Are Associated with Thyroid Associated Ophthalmopathy.

PURPOSE: To investigate the change of IL-10 producing regulatory B cells (Bregs), which function to suppress peripheral immune responses, in patients with thyroid associated ophthalmopathy (TAO).

METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy controls (N=54), patients with Grave's disease (N=26), and TAO patients (N=125), and stimulated with CpG/CD40L. The frequency of IL-10 producing Bregs and the expression of IL-10 in response to thyroid-stimulating hormone (TSH) stimulation were measured by flow cytometry. CD4+ T cells were cultured with Breg-depleted PBMCs to elucidate the function of Bregs in TAO patients. The potential immunoregulatory mechanism was also investigated by western blot and chromatin immunoprecipitation assays.

RESULTS: Active TAO patients had higher baseline levels of Bregs in their peripheral blood than both healthy controls and inactive patients. TSH promoted Bregs. Bregs from TAO patients were defective in suppressing the activation of IFN-γ+ and IL-17+ T cells in vitro.

CONCLUSIONS: We found that regulatory B cells in TAO patients are functionally defective, suggesting the defective Bregs might be responsible for the pathogenesis of TAO.