V(D)J Recombination: Orchestrating Diversity Without Damage

International audience; V(D)J recombination assembles immunoglobulin and T-cell receptor genes from the preexisting variable (V), diversity (D), and joining (J) gene segments by a cut and paste mechanism. While this receptor diversification strategy enables efficient immune responses against pathogens, it also poses a constant threat to the genome integrity. Tight regulation of this process at multiple levels is therefore critical to prevent genomic instability and neoplastic transformation. In this article, we discuss the temporal and spatial regulation of V(D)J recombination, in addition to the molecular mechanisms that regulate this process. Finally, we discuss the implication of V(D)J recombination in malignancies of the immune system. “RAGs are the end-point of the strategies developed through evolution to achieve the anticipatory “Promethean” recognition of all universal molecular forms”. – A.A. de Freitas, Tractus Immuno-Logicus.