Thyroid hormone induces B cells abnormal differentiation via overexpression of B cell-activating factor

Breakdown of tolerance and abnormal activation in B cells is an important mechanism in Graves disease (GD) pathogenesis. However, the mechanism by which B cells are abnormal differentiated and activated in GD remains elusive. Here, we show that elevated BAFF expression is positively correlated with serum thyroid hormone (TH) levels in GD patients and high TH levels can induce BAFF overexpression and lead to the abnormal differentiation of B cells in mice. This BAFF overexpression can be seen in many tissues. In the spleens of mice, high TH levels induce M1 macrophages polarization, which generates BAFF overexpression. Our findings open a new perspective on the interactions between endocrine and immune system and provide insight into the involvement of thyroid hormones in the development and progression of GD.