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

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.

Pubmed ID: 22431510

Authors

  • Gy├Âry I
  • Boller S
  • Nechanitzky R
  • Mandel E
  • Pott S
  • Liu E
  • Grosschedl R

Journal

Genes & development

Publication Data

April 1, 2012

Associated Grants

None

Mesh Terms

  • Animals
  • B-Lymphocytes
  • Cell Differentiation
  • Cell Proliferation
  • Cell Survival
  • Gene Expression Regulation
  • Genome-Wide Association Study
  • Immunoglobulin Heavy Chains
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Signal Transduction
  • Trans-Activators
  • Transcription, Genetic