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

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

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206 Scopus citations

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-α. 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.

Original languageEnglish (US)
Pages (from-to)1388-1398
Number of pages11
JournalNature Immunology
Volume9
Issue number12
DOIs
StatePublished - Oct 31 2008

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Dengler, H. S., Baracho, G. V., Omori, S. A., Bruckner, S., Arden, K. C., Castrillon, D. H., DePinho, R. A., & Rickert, R. C. (2008). Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. Nature Immunology, 9(12), 1388-1398. https://doi.org/10.1038/ni.1667