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Nat Immunol. 2010 Feb;11(2):171-9. doi: 10.1038/ni.1827. Epub 2009 Nov 29.

Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development.

Author information

1
Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria.

Abstract

STAT5 and interleukin 7 (IL-7) signaling are thought to control B lymphopoiesis by regulating the expression of key transcription factors and by activating variable (V(H)) gene segments at the immunoglobulin heavy-chain (Igh) locus. Using conditional mutagenesis to delete the gene encoding the transcription factor STAT5, we demonstrate that the development of pro-B cells was restored by transgenic expression of the prosurvival protein Bcl-2, which compensated for loss of the antiapoptotic protein Mcl-1. Expression of the genes encoding the B cell-specification factor EBF1 and the B cell-commitment protein Pax5 as well as V(H) gene recombination were normal in STAT5- or IL-7 receptor alpha-chain (IL-7Ralpha)-deficient pro-B cells rescued by Bcl-2. STAT5-expressing pro-B cells contained little or no active chromatin at most V(H) genes. In contrast, rearrangements of the immunoglobulin-kappa light-chain locus (Igk) were more abundant in STAT5- or IL-7Ralpha-deficient pro-B cells. Hence, STAT5 and IL-7 signaling control cell survival and the developmental ordering of immunoglobulin gene rearrangements by suppressing premature Igk recombination in pro-B cells.

PMID:
19946273
PMCID:
PMC2956121
DOI:
10.1038/ni.1827
[Indexed for MEDLINE]
Free PMC Article

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