Regulation of Marginal Zone B-Cell Differentiation by MicroRNA-146a
Jennifer K King1, Nolan M Ung2, May H Paing2
1Division of Rheumatology and STAR Program, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA; Cellular and Molecular Pathology Ph.D.Program, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA.
Abstract:
B-cell development in the bone marrow is followed by specification into functional subsets in the spleen, including marginal zone (MZ) B-cells. MZ B-cells are classically characterized by T-independent antigenic responses and require the elaboration of distinct gene expression programs for development. Given their role in gene regulation, it is not surprising that microRNAs are important factors in B-cell development. Recent work demonstrated that deficiency of the NFκB feedback regulator, miR-146a, led to a range of hematopoietic phenotypes, but B-cell phenotypes have not been extensively characterized. Here, we found that miR-146a-deficient mice demonstrate a reduction in MZ B-cells, likely from a developmental block. Utilizing high-throughput sequencing and comparative analysis of developmental stage-specific transcriptomes, we determined that MZ cell differentiation was impaired due to decreases in Notch2 signaling. Our studies reveal miR-146a-dependent B-cell phenotypes and highlight the complex role of miR-146a in the hematopoietic system.
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