Gullickson Peter, Xu Yunwen W, Niedernhofer Laura J, Thompson Elizabeth L, Yousefzadeh Matthew J
Department of Biochemistry, Institute on the Biology of Aging and Metabolism, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, United States.
Front Immunol. 2022 Apr 1;13:834889. doi: 10.3389/fimmu.2022.834889. eCollection 2022.
An effective humoral immune response necessitates the generation of diverse and high-affinity antibodies to neutralize pathogens and their products. To generate this assorted immune repertoire, DNA damage is introduced at specific regions of the genome. Purposeful genotoxic insults are needed for the successful completion of multiple immunological diversity processes: V(D)J recombination, class-switch recombination, and somatic hypermutation. These three processes, in concert, yield a broad but highly specific immune response. This review highlights the importance of DNA repair mechanisms involved in each of these processes and the catastrophic diseases that arise from DNA repair deficiencies impacting immune system function. These DNA repair disorders underline not only the importance of maintaining genomic integrity for preventing disease but also for robust adaptive immunity.
有效的体液免疫反应需要产生多样化且高亲和力的抗体来中和病原体及其产物。为了产生这种多样化的免疫库,基因组的特定区域会引入DNA损伤。成功完成多种免疫多样性过程(V(D)J重组、类别转换重组和体细胞超突变)需要有针对性的基因毒性损伤。这三个过程协同作用,产生广泛但高度特异性的免疫反应。本综述强调了参与这些过程的DNA修复机制的重要性,以及因DNA修复缺陷影响免疫系统功能而引发的灾难性疾病。这些DNA修复障碍不仅突显了维持基因组完整性对预防疾病的重要性,也突显了其对强大的适应性免疫的重要性。