The Bloom's Syndrome Helicase Is Critical for Development and Function of the αβ T-Cell Lineage
| Autor: | Philip Leder, Boris Reizis, Nicholas Chester, Holger Babbe |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Receptors Antigen T-Cell alpha-beta T-Lymphocytes T cell Mice Transgenic Thymus Gland Mice Immune system medicine Animals Cell Lineage Molecular Biology Gene Alleles Cells Cultured Immunodeficiency Adenosine Triphosphatases Chromosome Aberrations Mice Knockout RecQ Helicases biology urogenital system T-cell receptor DNA Helicases Genetic disorder nutritional and metabolic diseases Helicase Articles Cell Biology medicine.disease Molecular biology medicine.anatomical_structure biology.protein CD8 |
| Zdroj: | Molecular and Cellular Biology. 27:1947-1959 |
| ISSN: | 1098-5549 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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