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

Györy, I., Boller, S., Nechanitzky, R., Mandel, E., Pott, S., Liu, E., et al. (2012). Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferation, and survival of B cells. Genes and Development, 26, 668-682. doi:10.1101/gad.187328.112.

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Gyoery 2012_Genes Dev.pdf (Publisher version), 4MB
 
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http://genesdev.cshlp.org/content/26/7/668 (Publisher version)
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 Creators:
Györy, Ildiko1, Author              
Boller, Sören1, Author              
Nechanitzky, Robert1, Author              
Mandel, Elizabeth1, Author              
Pott, Sebastian2, Author
Liu, Edison2, Author
Grosschedl, Rudolf1, Author              
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2External Organizations, ou_persistent22              

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Free keywords: Ebf1; c-Myb; B-cell differentiation; BCR signaling; Ig class switch recombination; germinal center B cells
 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 Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. 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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Language(s): eng - English
 Dates: 2012-04-01
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1101/gad.187328.112
 Degree: -

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Title: Genes and Development
Source Genre: Journal
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Publ. Info: Cold Spring Harbor Laboratory Press
Pages: - Volume / Issue: 26 Sequence Number: - Start / End Page: 668 - 682 Identifier: ISSN: 0890-9369
CoNE: https://pure.mpg.de/cone/journals/resource/954925557453