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

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.

SUBMITTER: Dengler HS

PROVIDER: S-EPMC2679692 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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

Dengler Hart S HS Baracho Gisele V GV Omori Sidne A SA Bruckner Shane S Arden Karen C KC Castrillon Diego H DH DePinho Ronald A RA Rickert Robert C RC

Nature immunology 20081102 12

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. ...[more]

PMID: 18978794

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

Publications

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

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