Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros
| Autor: | Eric Bertolino, Zhengshan Chen, Karen L. Reddy, Ignacio A. Demarco, Damien Reynaud, Stephen T. Smale, Susan Winandy, Harinder Singh, Hilde Schjerven |
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| Rok vydání: | 2008 |
| Předmět: |
Cellular differentiation
Immunology chemical and pharmacologic phenomena Biology Article CD19 Cell Line Ikaros Transcription Factor Mice hemic and lymphatic diseases medicine Animals Immunology and Allergy Cell Lineage VDJ Recombinases Transcription factor B cell Gene Rearrangement Genetics B-Lymphocytes Binding Sites Genes Immunoglobulin Cell Differentiation TCF4 Gene rearrangement medicine.anatomical_structure biology.protein Immunoglobulin heavy chain Immunoglobulin Heavy Chains |
| Zdroj: | Nature Immunology. 9:927-936 |
| ISSN: | 1529-2916 1529-2908 |
| DOI: | 10.1038/ni.1626 |
| Popis: | The transcription factor Ikaros is essential for B cell development. However, its molecular functions in B cell fate specification and commitment have remained elusive. We show here that the transcription factor EBF restored the generation of CD19(+) pro-B cells from Ikaros-deficient hematopoietic progenitors. Notably, these pro-B cells, despite having normal expression of the transcription factors EBF and Pax5, were not committed to the B cell fate. They also failed to recombine variable gene segments at the immunoglobulin heavy-chain locus. Ikaros promoted heavy-chain gene rearrangements by inducing expression of the recombination-activating genes as well as by controlling accessibility of the variable gene segments and compaction of the immunoglobulin heavy-chain locus. Thus, Ikaros is an obligate component of a network that regulates B cell fate commitment and immunoglobulin heavy-chain gene recombination. |
| Databáze: | OpenAIRE |
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