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

Document Type

Article

Publication Date

4-1-2012

Keywords

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

JAX Source

Genes Dev 2012 Apr 1; 26(7):668-82.

PMID

22431510

Volume

26

Issue

7

First Page

668

Last Page

682

ISSN

1549-5477

Abstract

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.

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