B Lymphocytes Impede Tregs to Erode Islet Tolerance in Type 1 Diabetes.

ARTICLE HIGHLIGHTS: This study expands the role of B lymphocytes in type 1 diabetes by demonstrating how B cells influence the development and function of regulatory T cells (Tregs) during islet transplant and autoimmune progression. This study was done to explain how B lymphocytes regulate the progression of anti-islet immunity, even when they appear dispensable for effector cell activation. B-cell deficiency (using NOD.μMT mice) enables durable islet transplant tolerance, enhances the expansion of Helios+ Tregs, increases the ratio of insulin-reactive Tregs to effector T cells, and enhances islet-protective Treg function. These findings indicate that B lymphocytes accelerate destructive immunity by negatively regulating Treg development and function. Targeting the harmful B-cell-Treg interactions, particularly in the thymic environment, may offer new, more selective therapeutic strategies to prevent anti-islet immunity.