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Regulation of Marginal Zone B-Cell Differentiation by MicroRNA-146a

2017; Frontiers Media; Volume: 7; Linguagem: Inglês

10.3389/fimmu.2016.00670

1664-3224

Jennifer K. King, Nolan Ung, May Paing, Jorge R. Contreras, Michael O. Alberti, Thilini R. Fernando, Kelvin Zhang, Matteo Pellegrini, Dinesh S. Rao,

Immune Cell Function and Interaction

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.