Regulation of B cell tolerance and autoimmunity by miR-130b

Autoimmune diseases represent a timely health challenge due to their increasing incidence and lack of definitive cures. Autoreactive B cells play essential roles in several autoimmune diseases, including lupus erythematosus, rheumatoid arthritis and multiple sclerosis. However, the molecular mechanisms regulating these cells remain largely unknown. In this study, we identified miR-130b as a critical regulator of B cell tolerance through an unbiased bioinformatic motif enrichment analysis of lymphocyte-expressed miRNAs. Elevated levels of miR-130b impaired the elimination of autoreactive B cells during their development, enabling their escape to peripheral tissues. Mechanistically, miR-130b hindered clonal deletion by suppressing the expression of its targets Estrogen receptor alpha (ERα) and PTEN. Notably, ERα deficiency alone was sufficient to compromise B cell tolerance, allowing autoreactive B cells to reach the periphery, where they can contribute to the development and progression of autoimmune diseases. Overall, this study advances our understanding of B cell tolerance and provides new insights into the gender differences frequently observed in autoimmunity. The identification of miR-130b and ERα as regulators of B cell tolerance opens new avenues to improve the diagnosis and treatment of autoimmune diseases.