| First Author | Debnath I | Year | 2013 |
| Journal | Int Immunol | Volume | 25 |
| Issue | 2 | Pages | 99-115 |
| PubMed ID | 23087187 | Mgi Jnum | J:192189 |
| Mgi Id | MGI:5464153 | Doi | 10.1093/intimm/dxs088 |
| Citation | Debnath I, et al. (2013) Bone marrow-induced Mef2c deficiency delays B-cell development and alters the expression of key B-cell regulatory proteins. Int Immunol 25(2):99-115 |
| abstractText | 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. |
