Danska J S, Pflumio F, Williams C J, Huner O, Dick J E, Guidos C J
Division of Surgical Research, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Science. 1994 Oct 21;266(5184):450-5. doi: 10.1126/science.7524150.
Assembly of antigen receptor V (variable), D (diversity), and J (joining) gene segments requires lymphocyte-specific genes and ubiquitous DNA repair activities. Severe combined immunodeficient (SCID) mice are defective in general double-strand (ds) DNA break repair and V(D)J coding joint formation, resulting in arrested lymphocyte development. A single treatment of newborn SCID mice with DNA-damaging agents restored functional, diverse, T cell receptor beta chain coding joints, as well as development and expansion of thymocytes expressing both CD4 and CD8 coreceptors, but did not promote B cell development. Thymic lymphoma developed in all mice treated with DNA-damaging agents, suggesting an interrelation between V(D)J recombination, dsDNA break repair, and lymphomagenesis.
抗原受体V（可变）、D（多样）和J（连接）基因片段的组装需要淋巴细胞特异性基因和普遍存在的DNA修复活性。重症联合免疫缺陷（SCID）小鼠在一般双链（ds）DNA断裂修复和V（D）J编码接头形成方面存在缺陷，导致淋巴细胞发育停滞。用DNA损伤剂对新生SCID小鼠进行单次治疗可恢复功能性、多样化的T细胞受体β链编码接头，以及表达CD4和CD8共受体的胸腺细胞的发育和扩增，但不促进B细胞发育。在用DNA损伤剂治疗的所有小鼠中都发生了胸腺淋巴瘤，这表明V（D）J重组、dsDNA断裂修复和淋巴瘤发生之间存在相互关系。
