| First Author | Hamrouni A | Year | 2007 |
| Journal | Eur J Immunol | Volume | 37 |
| Issue | 7 | Pages | 1978-85 |
| PubMed ID | 17559169 | Mgi Jnum | J:123493 |
| Mgi Id | MGI:3718737 | Doi | 10.1002/eji.200636632 |
| Citation | Hamrouni A, et al. (2007) Impact of cellular lifespan on the T cell receptor repertoire. Eur J Immunol 37(7):1978-85 |
| abstractText | Pro-survival members of the Bcl-2 family are potent inhibitors of cell death and determine the lifespan of immature thymocytes by counteracting the intrinsically active apoptotic program in these cells. BH3-only proteins are potent antagonists of Bcl-2-like molecules and regulate death and survival of lymphocytes during their development and homeostasis. The intrinsic lifespan of CD4(+)8(+) double-positive thymocytes was reported to actively shape the diversity of the immune repertoire, since mice overexpressing Bcl-x(L) were reported to show a bias towards the usage of distal 3' Jalpha elements 1. To gain support for this concept, we analyzed TCRalpha rearrangements in T lymphocytes that show an extended lifespan due to either loss of the BH3-only protein Bim or overexpression of Bcl-2. A minor but reproducible skewing towards the usage of the more distal 3' Jalpha elements was observed in developing thymocytes and mature T cells from bim(-/-) and vav-bcl-2 transgenic mice, indicating that prolonged survival of double-positive thymocytes does have a significant impact on the selected TCRalpha repertoire. However, the changes that we observed were less pronounced than those found in lck-bcl-x(L) transgenic mice, pointing towards qualitative differences between Bcl-2- and Bcl-x(L)-mediated cell death inhibition during T cell development. |
