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Nat Immunol. 2008 Dec;9(12):1388-98. doi: 10.1038/ni.1667. Epub 2008 Nov 2.

Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation.

Author information

1
Program of Inflammatory Disease Research, Burnham Institute for Medical Research, La Jolla, California 92037, USA.

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.

PMID:
18978794
PMCID:
PMC2679692
DOI:
10.1038/ni.1667
[Indexed for MEDLINE]
Free PMC Article

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