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

Research output: Contribution to journalArticle

196 Citations (Scopus)

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 - 2008

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Cell Differentiation
B-Lymphocytes
Transcription Factors
B-Lymphoid Precursor Cells
Genetic Recombination
Interleukin-7 Receptors
L-Selectin
Transcriptional Activation
Up-Regulation
Lymph Nodes
Gene Expression
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Dengler, H. S., Baracho, G. V., Omori, S. A., Bruckner, S., Arden, K. C., Castrillon, D. H., ... 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

Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. / Dengler, Hart S.; Baracho, Gisele V.; Omori, Sidne A.; Bruckner, Shane; Arden, Karen C.; Castrillon, Diego H.; DePinho, Ronald A.; Rickert, Robert C.

In: Nature Immunology, Vol. 9, No. 12, 2008, p. 1388-1398.

Research output: Contribution to journalArticle

Dengler, HS, Baracho, GV, Omori, SA, Bruckner, S, Arden, KC, Castrillon, DH, DePinho, RA & Rickert, RC 2008, 'Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation', Nature Immunology, vol. 9, no. 12, pp. 1388-1398. https://doi.org/10.1038/ni.1667
Dengler, Hart S. ; Baracho, Gisele V. ; Omori, Sidne A. ; Bruckner, Shane ; Arden, Karen C. ; Castrillon, Diego H. ; DePinho, Ronald A. ; Rickert, Robert C. / Distinct functions for the transcription factor Foxo1 at various stages of B cell differentiation. In: Nature Immunology. 2008 ; Vol. 9, No. 12. pp. 1388-1398.
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