RESCUE OF T-CELL-SPECIFIC V(D)J RECOMBINATION IN SCID MICE BY DNA-DAMAGING AGENTS

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 oi 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.