Journal Article

Bone marrow-induced Mef2c deficiency delays B-cell development and alters the expression of key B-cell regulatory proteins

Irina Debnath, Kirstin M. Roundy, Peter D. Pioli, Janis J. Weis and John H. Weis

in International Immunology

Volume 25, issue 2, pages 99-115
Published in print February 2013 | ISSN: 0953-8178
Published online October 2012 | e-ISSN: 1460-2377 | DOI: http://dx.doi.org/10.1093/intimm/dxs088
Bone marrow-induced Mef2c deficiency delays B-cell development and alters the expression of key B-cell regulatory proteins

More Like This

Show all results sharing these subjects:

  • Immunology
  • Biological Sciences

GO

Show Summary Details

Preview

The Mef2 family transcriptional regulator Mef2c (myocyte enhancer factor 2c) is highly expressed in maturing bone marrow and peripheral mature B-cells. To evaluate the role of this transcription factor in B-cell development, we generated a B-cell-specific conditional deletion of Mef2c using the Mb-1-Cre transgene that is expressed during the early stages of immunoglobulin rearrangement. Young mice possessing this defect demonstrated a significant impairment in B-cell numbers in bone marrow and spleen. This phenotype was evident in all B-cell subsets; however, as the animals mature, the deficit in the peripheral mature B-cell compartments was overcome. The absence of Mef2c in mature B-cells led to unique CD23+ and CD23 subsets that were evident in Mef2c knockout primary samples as well as Mef2c-deficient cultured, differentiated B-cells. Genome-wide expression analysis of immature and mature B-cells lacking Mef2c indicated altered expression for a number of key regulatory proteins for B-cell function including Ciita, CD23, Cr1/Cr2 and Tnfsf4. Chromatin immunoprecipitation analysis confirmed Mef2c binding to the promoters of these genes indicating a direct link between the presence (or absence) of Mef2c and altered transcriptional control in mature B-cells.

Keywords: B-cells; differentiation; gene expression; Mef2c; mouse

Journal Article.  10219 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.