<b>B lymphocytes impede Tregs to erode islet tolerance in Type 1 Diabetes</b>

<p dir="ltr">B lymphocytes are thought to drive beta cell destruction in type 1 diabetes by activating anti-islet T cells. However, the observation that autoreactive T cell activation and disease progression can occur without B cells challenges this view. Still, preclinical and clinical studies show that B cell depletion alleviates beta cell destruction, suggesting a critical role for B cells in T1D. Our findings propose an alternative function for B cells—impairing regulatory T cells that would otherwise protect islets. In the NOD islet transplant model, we show that B cell absence enables transplantation tolerance, allowing Tregs to become responsive to immune therapy and confer allograft protection. Extending this to spontaneous diabetes, we find that insulin-reactive Tregs are reduced in NOD mice in proportion to insulin-reactive B cells, while effector T cells remain unaffected. Moreover, Tregs from B cell-deficient NOD mice better restrain beta cell destruction than those from B cell-sufficient environments. Together, these findings indicate that autoreactive B cells primarily erode immune regulation by culling islet-protective Tregs. Thus, therapies that mobilize Tregs could be more effective when combined with B cell-targeting strategies in islet transplantation or type 1 diabetes prevention.</p>