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 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.
Danska
J S
JS
Division of Surgical Research, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada.
Pflumio
F
F
Williams
C J
CJ
Huner
O
O
Dick
J E
JE
Guidos
C J
CJ
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001483:Base Sequence; D001761:Bleomycin / Q000494:pharmacology; D002471:Cell Transformation, Neoplastic; D004249:DNA Damage; D004260:DNA Repair; D005720:Gamma Rays; D015321:Gene Rearrangement; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology; D008223:Lymphoma / Q000209:etiology / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D008969:Molecular Sequence Data; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D013953:Thymus Neoplasms / Q000209:etiology / Q000473:pathology
D016693:Receptors, Antigen, T-Cell, alpha-beta; D001761:Bleomycin