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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Blotting, Southern
  • Cell Differentiation / immunology*
  • DNA-Binding Proteins / immunology
  • DNA-Binding Proteins / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / immunology*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression / immunology
  • Gene Rearrangement, B-Lymphocyte / genetics
  • Homeodomain Proteins / immunology
  • Homeodomain Proteins / metabolism
  • Immunohistochemistry
  • Mice
  • Mice, Mutant Strains
  • Reverse Transcriptase Polymerase Chain Reaction
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • Transcription, Genetic / immunology


  • DNA-Binding Proteins
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • Foxo1 protein, mouse
  • Homeodomain Proteins
  • Rag2 protein, mouse
  • RAG-1 protein