title: STAT5 regulates the self-renewal capacity and differentiation of human memory B cells and controls Bcl-6 expression.
abstract: 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.
authors.affiliation: Department of Cell Biology and Histology of the Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, Netherlands.
authors.forename: Ferenc A
authors.initials: FA
authors.lastname: Scheeren
authors.forename: Marianne
authors.initials: M
authors.lastname: Naspetti
authors.forename: Sean
authors.initials: S
authors.lastname: Diehl
authors.forename: Remko
authors.initials: R
authors.lastname: Schotte
authors.forename: Maho
authors.initials: M
authors.lastname: Nagasawa
authors.forename: Erwin
authors.initials: E
authors.lastname: Wijnands
authors.forename: Ramon
authors.initials: R
authors.lastname: Gimeno
authors.forename: Florry A
authors.initials: FA
authors.lastname: Vyth-Dreese
authors.forename: Bianca
authors.initials: B
authors.lastname: Blom
authors.forename: Hergen
authors.initials: H
authors.lastname: Spits
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007156:Immunologic Memory; D008894:Milk Proteins / Q000187:drug effects / Q000378:metabolism*; D051560:Proto-Oncogene Proteins c-bcl-6; D050799:STAT5 Transcription Factor; D013629:Tamoxifen / Q000494:pharmacology; D015534:Trans-Activators / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D008894:Milk Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D015534:Trans-Activators; D013629:Tamoxifen