| First Author | Collins B | Year | 2013 |
| Journal | Eur J Immunol | Volume | 43 |
| Issue | 2 | Pages | 521-32 |
| PubMed ID | 23172374 | Mgi Jnum | J:192814 |
| Mgi Id | MGI:5466614 | Doi | 10.1002/eji.201242757 |
| Citation | Collins B, et al. (2013) Ikaros promotes rearrangement of TCR alpha genes in an Ikaros null thymoma cell line. Eur J Immunol 43(2):521-32 |
| abstractText | 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 beta gene rearrangement and expresses a surface pre-TCR. JE131 cells also carry nonfunctional rearrangements on both alleles of their TCR alpha loci. Retroviral reintroduction of Ikaros dramatically increased the rate of transcription in the alpha locus and TCR Valpha/Jalpha recombination resulting in the appearance of many new alphabetaTCR(+) cells. The process is RAG dependent, requires switch/sucrose nonfermentable chromatin-remodeling complexes and is coincident with the binding of Ikaros to the TCR alpha enhancer. Furthermore, knockdown of Mi2/nucleosome remodeling and deacetylase complexes increased the frequency of TCR alpha rearrangement. Our data suggest that Ikaros controls Valpha/Jalpha recombination in T cells by controlling access of the transcription and recombination machinery to the TCR alpha 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 alphabetaTCR(+) CD4(+) CD8(+) thymocyte transition. |
