| First Author | Babbe H | Year | 2007 |
| Journal | Mol Cell Biol | Volume | 27 |
| Issue | 5 | Pages | 1947-59 |
| PubMed ID | 17210642 | Mgi Jnum | J:118992 |
| Mgi Id | MGI:3700903 | Doi | 10.1128/MCB.01402-06 |
| Citation | Babbe H, et al. (2007) The Bloom's syndrome helicase is critical for development and function of the alphabeta T-cell lineage. Mol Cell Biol 27(5):1947-59 |
| abstractText | Bloom's syndrome is a genetic disorder characterized by increased incidence of cancer and an immunodeficiency of unknown origin. The BLM gene mutated in Bloom's syndrome encodes a DNA helicase involved in the maintenance of genomic integrity. To explore the role of BLM in the immune system, we ablated murine Blm in the T-cell lineage. In the absence of Blm, thymocytes were severely reduced in numbers and displayed a developmental block at the beta-selection checkpoint that was partially p53 dependent. Blm-deficient thymocytes rearranged their T-cell receptor (TCR) beta genes normally yet failed to survive and proliferate in response to pre-TCR signaling. Furthermore, peripheral T cells were reduced in numbers, manifested defective homeostatic and TCR-induced proliferation, and produced extensive chromosomal damage. Finally, CD4(+) and CD8(+) T-cell responses were impaired upon antigen challenge. Thus, by ensuring genomic stability, Blm serves a vital role for development, maintenance, and function of T lymphocytes, suggesting a basis for the immune deficiency in Bloom's syndrome. |
