The microRNA-212/132 cluster regulates B cell development and apoptosis by targeting SOX4

MicroRNAs have emerged as key regulators of B cell fate decisions and immune function. Deregulation of several microRNAs in B cells leads to the development of autoimmune disease and cancer in mice. We demonstrate that the microRNA-212/132 cluster (miR-212/132) is induced in B cells in response to B cell receptor signaling. Enforced expression of miR-132 results in a block in early B cell development at the pre-pro-B cell to pro-B cell transition and induces apoptosis in primary bone marrow B cells. Importantly, loss of miR-212/132 results in increased B cell output under non-homeostatic conditions. We find that miR-212/132 regulates B lymphopoiesis by targeting the transcription factor SOX4. Co-expression of SOX4 with miR-132 rescues the defect in B cell development from over-expression of miR-132 alone. In addition, we show that the expression of miR-132 in cells that are prone to spontaneous B cell cancers can have a protective effect on cancer development. We have thus uncovered a novel regulator of B cell lineage specification that may potential applications in B cell cancer therapy Overall design: RNA-seq of wild-type and microRNA-212/132 knock-out B-cells after IgM stimulation

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Mehta A, Mann M, Zhao JL, Marinov GK, Majumdar D, Garcia-Flores Y, Du X, Erikci E, Chowdhury K, Baltimore D