Role of STAT5 in controlling cell survival and immunoglobulin gene recombination during pro-B cell development
- Author(s)
- Malin, S; McManus, S; Cobaleda, C; Novatchkova, M; Delogu, A; Bouillet, P; Strasser, A; Busslinger, M;
- Details
- Publication Year 2010-02,Volume 11,Issue #2,Page 171-U97
- Journal Title
- NATURE IMMUNOLOGY
- Publication Type
- Journal Article
- 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-7R alpha)-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-7R alpha-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.
- Publisher
- NATURE PUBLISHING GROUP
- Keywords
- RECEPTOR-DEFICIENT MICE; HEAVY-CHAIN GENE; COMMON LYMPHOID PROGENITORS; MURINE BONE-MARROW; IL-7 RECEPTOR; BCL-X; LINEAGE DIFFERENTIATION; INDUCED TRANSFORMATION; TRANSCRIPTION; INTERLEUKIN-7
- Publisher's Version
- https://doi.org/10.1038/ni.1827
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2010-02-01 12:00:00