Immune diversity and genomic stability: opposite goals but similar paths

DNA damage response mechanisms serve to protect cells from exogenous and endogenous DNA damaging agents with the aim of maintaining genomic stability. In contrast, the generation of an efficient immune response requires the creation of a repertoire of distinct immunoglobulin and T cell receptor genes able to recognise the huge array of antigens that may be encountered in a lifetime. Surprisingly, cells have exploited the same mechanisms used to maintain genomic integrity to create genetic diversity during immune development. Here, we review the damage response mechanisms operating on DNA double strand breaks and their function during development of the immune response. We discuss disorders that are associated with immunodeficiency and defective responses to the presence of DNA double strand breaks.