Ikaros promotes rearrangement of TCR α genes in an Ikaros null thymoma cell line.
Eur J Immunol
; 43(2): 521-32, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-23172374
ABSTRACT
Ikaros is important in the development and maintenance of the lymphoid system, functioning in part by associating with chromatin-remodeling complexes. We have studied the functions of Ikaros in the transition from pre-T cell to the CD4(+) CD8(+) thymocyte using an Ikaros null CD4(-) CD8(-) mouse thymoma cell line (JE131). We demonstrate that this cell line carries a single functional TCR ß gene rearrangement and expresses a surface pre-TCR. JE131 cells also carry nonfunctional rearrangements on both alleles of their TCR α loci. Retroviral reintroduction of Ikaros dramatically increased the rate of transcription in the α locus and TCR Vα/Jα recombination resulting in the appearance of many new αßTCR(+) cells. The process is RAG dependent, requires switch/sucrose nonfermentable chromatin-remodeling complexes and is coincident with the binding of Ikaros to the TCR α enhancer. Furthermore, knockdown of Mi2/nucleosome remodeling and deacetylase complexes increased the frequency of TCR α rearrangement. Our data suggest that Ikaros controls Vα/Jα recombination in T cells by controlling access of the transcription and recombination machinery to the TCR α loci. The JE131 cell line should prove to be a very useful tool for studying the molecular details of this and other processes involved in the pre-T cell to αßTCR(+) CD4(+) CD8(+) thymocyte transition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Timoma
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Linfócitos Nulos
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Receptores de Antígenos de Linfócitos T alfa-beta
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Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T
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Fator de Transcrição Ikaros
Limite:
Animals
Idioma:
En
Revista:
Eur J Immunol
Ano de publicação:
2013
Tipo de documento:
Article