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Review
Nature Reviews Immunology 3, 962–972 (1 December 2003) | doi:10.1038/nri1247
The mechanisms of immune diversification and their disorders
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Abstract
Three molecular mechanisms contribute to the diversity of the immune repertoire of B and T cells: V(D)J recombination generates the primary repertoire in both cases, whereas class-switch recombination (CSR) and somatic hypermutation (SHM) improve the quality of the B-cell response after antigen triggering. These three mechanisms involve marked DNA damage and modification, which require a fully competent cellular DNA-repair machinery. Defects in V(D)J recombination, CSR or SHM reactions lead to immune deficiencies, the study of which has allowed the identification of genes that are central to these processes. The inability to properly manage DNA damage/modification during V(D)J recombination, can also promote the development of cancer, as shown by the emergence of B-cell lymphomas in patients with a partial Artemis defect.
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