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

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

doi:10.3389/fimmu.2016.00670

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

Front Immunol. 2017 Jan 16:7:670. doi: 10.3389/fimmu.2016.00670. eCollection 2016.

Authors

Jennifer K King¹, Nolan M Ung², May H Paing², Jorge R Contreras³, Michael O Alberti², Thilini R Fernando², Kelvin Zhang⁴, Matteo Pellegrini⁵, Dinesh S Rao⁶

Affiliations

¹ Division 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.
² Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA , USA.
³ Cellular and Molecular Pathology Ph.D.Program, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, USA.
⁴ Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, USA; Howard Hughes Medical Institute, University of California Los Angeles, Los Angeles, CA, USA.
⁵ Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Molecular Cell and Developmental Biology, University of California Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, Los Angeles, CA, USA.
⁶ Department of Pathology and Laboratory Medicine, University of California Los Angeles, Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California Los Angeles, 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.

Keywords: B-cell development; gene regulation; marginal zone B-cells; microRNA; notch signaling.

Abstract

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