Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells

作者：Ildikó Győry, Sören Boller, Robert Nechanitzky, Elizabeth M. Mandel, Sebastian Pott, Edison Liu, Rudolf Grosschedl · 发表于：Genes & Development · 年份：2012 · DOI：10.1101/gad.187328.112 · 被引用次数：168 · 研究领域：T-cell and B-cell Immunology、NF-κB Signaling Pathways、Immune Cell Function and Interaction

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.