Distinct roles for Foxo1 at multiple stages of B cell differentiation View Full Text


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Article Info

DATE

2008-11-02

AUTHORS

Hart S. Dengler, Gisele V. Baracho, Sidne A. Omori, Shane Bruckner, Karen Arden, Diego H. Castrillon, Ronald A. DePinho, Robert C. Rickert

ABSTRACT

The transcription factors Foxo1, Foxo3 and Foxo4 modulate cell fate 'decisions' in diverse systems. Here we show that Foxo1-dependent gene expression was critical at many stages of B cell differentiation. Early deletion of Foxo1 caused a substantial block at the pro-B cell stage due to a failure to express interleukin 7 receptor-alpha. Foxo1 inactivation in late pro-B cells resulted in an arrest at the pre-B cell stage due to lower expression of the recombination-activating genes Rag1 and Rag2. Deletion of Foxo1 in peripheral B cells led to fewer lymph node B cells due to lower expression of L-selectin and failed class-switch recombination due to impaired upregulation of the gene encoding activation-induced cytidine deaminase. Thus, Foxo1 regulates a transcriptional program that is essential for early B cell development and peripheral B cell function. More... »

PAGES

1388-1398

References to SciGraph publications

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  • 2003-02-03. Pten inactivation alters peripheral B lymphocyte fate and reconstitutes CD19 function in NATURE IMMUNOLOGY
  • 2008-05-11. Foxo1 directly regulates the transcription of recombination-activating genes during B cell development in NATURE IMMUNOLOGY
  • 2002-04-22. Essential roles of the κ light chain intronic enhancer and 3′ enhancer in κ rearrangement and demethylation in NATURE IMMUNOLOGY
  • 2003-04-28. E-proteins directly regulate expression of activation-induced deaminase in mature B cells in NATURE IMMUNOLOGY
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  • 2008-06-22. Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros in NATURE IMMUNOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ni.1667

    DOI

    http://dx.doi.org/10.1038/ni.1667

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18978794


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