STAT5 regulates the self-renewal capacity and differentiation of human memory B cells and controls Bcl-6 expression

Nat Immunol. 2005 Mar;6(3):303-13. doi: 10.1038/ni1172. Epub 2005 Feb 13.


It is unknown how B cells that mature during a germinal center reaction 'decide' between plasma or memory cell fate. Here we describe a previously unknown subpopulation of B cells in the human germinal center that is characterized by tyrosine phosphorylated transcriptional activator STAT5. These cells had an activated centrocyte phenotype and had abundant expression of BCL6 but low expression of PRDM1, both encoding transcriptional repression proteins. Using RNA interference and ectopic expression of constitutively activated forms of STAT5, we demonstrate here a function for STAT5 in the self-renewal of B cells in vitro. STAT5b isoform seemed to directly upregulate Bcl-6, and ectopic expression of Bcl-6 in B cells resulted in self-renewal and inhibition of plasma cell differentiation. These data indicate that activation of STAT5 is involved in regulation of memory B cell differentiation.

MeSH terms

  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • Cell Differentiation
  • DNA-Binding Proteins / drug effects
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Immunologic Memory*
  • Milk Proteins / drug effects
  • Milk Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-6
  • STAT5 Transcription Factor
  • Tamoxifen / pharmacology
  • Trans-Activators / drug effects
  • Trans-Activators / metabolism*
  • Up-Regulation


  • BCL6 protein, human
  • DNA-Binding Proteins
  • Milk Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • STAT5 Transcription Factor
  • STAT5B protein, human
  • Trans-Activators
  • Tamoxifen