Characterization of Regulatory B Cells in Graves’ Disease and Hashimoto’s Thyroiditis

A hallmark of regulatory B cells is IL-10 production, hence their designation as IL-10(+) B cells. Little is known about the ability of self-antigens to induce IL-10(+) B cells in Graves’ disease (GD), Hashimoto’s thyroiditis (HT), or other autoimmune disease. Here we pulsed purified B cells from 12 HT patients, 12 GD patients, and 12 healthy donors with the thyroid self-antigen, thyroglobulin (TG) and added the B cells back to the remaining peripheral blood mononuclear cells (PBMCs). This procedure induced IL-10(+) B-cell differentiation in GD. A similar tendency was observed in healthy donors, but not in cells from patients with HT. In GD, B cells primed with TG induced IL-10-producing CD4(+) T cells. To assess the maximal frequency of inducible IL-10(+) B cells in the three donor groups PBMCs were stimulated with PMA/ionomycin. The resulting IL-10(+) B-cell frequency was similar in the three groups and correlated with free T(3) levels in GD patients. IL-10(+) B cells from both patient groups displayed CD25 or TIM-1 more frequently than did those from healthy donors. B-cell expression of two surface marker combinations previously associated with regulatory B-cell functions, CD24(hi)CD38(hi) and CD27(+)CD43(+), did not differ between patients and healthy donors. In conclusion, our findings indicate that autoimmune thyroiditis is not associated with reduced frequency of IL-10(+) B cells. These results do not rule out regulatory B-cell dysfunction, however. The observed phenotypic differences between IL-10(+) B cells from patients and healthy donors are discussed.