title: Regulation of Marginal Zone B-Cell Differentiation by MicroRNA-146a.
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.
authors.affiliation: 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.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: King
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA , USA.
authors.forename: Nolan M
authors.initials: NM
authors.lastname: Ung
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA , USA.
authors.forename: May H
authors.initials: MH
authors.lastname: Paing
authors.affiliation: 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.
authors.forename: Jorge R
authors.initials: JR
authors.lastname: Contreras
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA , USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Alberti
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California Los Angeles , Los Angeles, CA , USA.
authors.forename: Thilini R
authors.initials: TR
authors.lastname: Fernando
authors.affiliation: 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.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.affiliation: 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.
authors.forename: Dinesh S
authors.initials: DS
authors.lastname: Rao
keywords: B-cell development; gene regulation; marginal zone B-cells; microRNA; notch signaling