Department of Paediatric Immunology, Newcastle General Hospital, Newcastle upon Tyne, UK.
Expert Rev Mol Med. 2010 Mar 18;12:e9. doi: 10.1017/S1462399410001419.
DNA-repair pathways recognise and repair DNA damaged by exogenous and endogenous agents to maintain genomic integrity. Defects in these pathways lead to replication errors, loss or rearrangement of genomic material and eventually cell death or carcinogenesis. The creation of diverse lymphocyte receptors to identify potential pathogens requires breaking and randomly resorting gene segments encoding antigen receptors. Subsequent repair of the gene segments utilises ubiquitous DNA-repair proteins. Individuals with defective repair pathways are found to be immunodeficient and many are radiosensitive. The role of repair proteins in the development of adaptive immunity by VDJ recombination, antibody isotype class switching and affinity maturation by somatic hypermutation has become clearer over the past few years, partly because of identification of the genes involved in human disease. We describe the mechanisms involved in the development of adaptive immunity relating to DNA repair, and the clinical consequences and treatment of the primary immunodeficiency resulting from such defects.
DNA 修复途径识别和修复由外源和内源因素引起的 DNA 损伤，以维持基因组完整性。这些途径的缺陷会导致复制错误、基因组物质的丢失或重排，最终导致细胞死亡或癌变。为了识别潜在的病原体，淋巴细胞受体需要不断产生多样性，这需要打破并随机重组编码抗原受体的基因片段。随后，利用普遍存在的 DNA 修复蛋白对基因片段进行修复。研究发现，具有缺陷修复途径的个体免疫功能缺陷，并且许多个体对辐射敏感。在过去的几年中，由于鉴定出与人类疾病相关的基因，修复蛋白在 VDJ 重组、抗体同种型转换和体细胞超突变导致的亲和力成熟等适应性免疫中的作用变得更加清晰。我们描述了与 DNA 修复相关的适应性免疫发展的机制，以及由这些缺陷引起的原发性免疫缺陷的临床后果和治疗方法。
