The microRNA-212/132 cluster regulates B cell development by setting a threshold for Sox4 expression

Abstract

MicroRNAs play unique roles as logic elements in B cell differentiation by allowing for fine-tuning of differentiation checkpoints. We have found that the miR-212/132 cluster is induced in B cells in response to anti-IgM stimulation and that it can regulate B cell differentiation by establishing a threshold of Sox4 expression necessary for progression of progenitor B cells. Over-expression of miR-132 blocks the transition of pre-pro-B cells to pro-B cells, in part by inducing apoptosis in primary bone marrow B cells. The deletion of miR-212/132 results in increased B cell output under conditions of inflammatory stress. We validate Sox4 as a novel target of miR-132, and show that co-expression of Sox4 with miR-132 can rescue the phenotype observed with over-expression of miR-132 alone. We further demonstrate that over-expression of miR-132 can inhibit the development of B cell leukemia in mice that have B cells expressing the c-myc oncogene. We have therefore described miR-212/132 as a novel regulator of B cell development through its regulation of Sox4 expression.

Additional details