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- Title
Ikaros promotes rearrangement of TCR α genes in an Ikaros null thymoma cell line.
- Authors
Collins, Bernard; Clambey, Eric T.; Scott‐Browne, James; White, Janice; Marrack, Philippa; Hagman, James; Kappler, John W.
- 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 β 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 αβ TCR+ 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 αβ TCR+ CD4+ CD8+ thymocyte transition.
- Publication
European Journal of Immunology, 2013, Vol 43, Issue 2, p521
- ISSN
0014-2980
- Publication type
Article
- DOI
10.1002/eji.201242757