The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity

Autoreactive B cells play critical roles in a large diversity of autoimmune diseases, but the molecular pathways controlling these cells remain poorly understood. We performed an in vivo functional screen of a lymphocyte-expressed miRNA library and identified the microRNA miR-148a as a potent regulator of B cell tolerance. Elevated miR-148a expression impaired B cell tolerance by promoting the survival of immature B cells upon B cell receptor engagement via suppressing the expression of Gadd45a, Pten and Bcl2l11, which encodes the pro-apoptotic factor Bim. Furthermore, increased expression of miR-148a, which occurs frequently in lupus patients and lupus-prone mice, facilitated the development of lethal autoimmune disease in a lupus mouse model. These studies demonstrate that miR-148a functions as an important regulator of B cell tolerance and autoimmunity.