First Author | Györy I | Year | 2012 |
Journal | Genes Dev | Volume | 26 |
Issue | 7 | Pages | 668-82 |
PubMed ID | 22431510 | Mgi Jnum | J:182210 |
Mgi Id | MGI:5315021 | Doi | 10.1101/gad.187328.112 |
Citation | Gyory I, et al. (2012) Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells. Genes Dev 26(7):668-82 |
abstractText | The transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into the functions of Ebf1 at distinct stages of differentiation, we conditionally inactivated Ebf1. We found that Ebf1 is required for the proliferation, survival, and signaling of pro-B cells and peripheral B-cell subsets, including B1 cells and marginal zone B cells. The proliferation defect of Ebf1-deficient pro-B cells and the impaired expression of multiple cell cycle regulators are overcome by transformation with v-Abl. The survival defect of transformed Ebf1(fl/fl) pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-x(L). In mature B cells, Ebf1 deficiency interferes with signaling via the B-cell-activating factor receptor (BAFF-R)- and B-cell receptor (BCR)-dependent Akt pathways. Moreover, Ebf1 is required for germinal center formation and class switch recombination. Genome-wide analyses of Ebf1-mediated gene expression and chromatin binding indicate that Ebf1 regulates both common and distinct sets of genes in early and late stage B cells. By regulating important components of transcription factor and signaling networks, Ebf1 appears to be involved in the coordination of cell proliferation, survival, and differentiation at multiple stages of B lymphopoiesis. |