V(D)J recombination and DNA repair: lessons from human immune deficiencies and other animal models.
OBJECTIVE
V(D)J recombination not only represents the main mechanism for the diversification of the immune system, it also constitutes a critical checkpoint in the development of both B and T lymphocytes. While a defect in V(D)J recombination leads to severe combined immune deficiency, a deregulation of this process can participate in the onset of lymphoid malignancies.


RESULTS
The careful analysis of human severe combined immune deficiency patients as well as engineered murine models provided several new interesting insights into the physiopathology of the V(D)J recombination process. A new factor of the V(D)J recombination/DNA repair machinery, Artemis, was identified based on its deficiency in human severe combined immune deficiency patients. It also became evident from knockout mouse studies that DNA repair factors that participate in V(D)J recombination can be considered as genomic caretakers.


CONCLUSIONS
While V(D)J recombination was first recognized as a critical checkpoint in the development of the immune system, the discovery of several DNA repair factors that participate in this reaction shed light on more general aspects of genomic stability and cancer predisposition.
de Villartay
Jean-Pierre
JP
Developpement Normal et Pathologie du système Immunataire, INSERM U429, Hôpital Necker Enfants-Malades, Paris, France. devillar@infobiogen.fr
D000818:Animals; D004260:DNA Repair; D004268:DNA-Binding Proteins; D004720:Endonucleases; D008040:Genetic Linkage; D023281:Genomics; D006801:Humans; D008223:Lymphoma / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D012680:Sensitivity and Specificity; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology*; D045567:VDJ Recombinases / Q000276:immunology* / Q000378:metabolism; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D045567:VDJ Recombinases; C426344:DCLRE1C protein, human; D004720:Endonucleases; D001618:beta-Lactamases