Center of Integrated Medical Research, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.
Int J Hematol. 2011 Apr;93(4):425-433. doi: 10.1007/s12185-011-0836-5. Epub 2011 Apr 12.
V(D)J recombination and class switch recombination are achieved by the cooperative processes of recombination activation gene- or activation-induced cytidine deaminase-dependent DNA cleaving, DNA double-strand break (DSB) response signaling, and DNA repair. Primary immunodeficiency due to dysfunctional DNA recombination can be categorized as severe combined immunodeficiency or other conditions, based on the presence or absence of T cells. We can also classify these diseases as radiosensitive or non-radiosensitive immunodeficiencies. While diseases unable to trigger DNA cleavage do not exhibit radiosensitivity, dysfunction in DSB response signaling or repair does lead to radiosensitive immunodeficiency. Recent studies have begun to clarify the mechanisms underlying the molecular pathogenesis of such DNA DSB-related primary immunodeficiency.
V(D)J 重组和类别转换重组是通过重组激活基因或激活诱导胞苷脱氨酶依赖性 DNA 切割、DNA 双链断裂 (DSB) 反应信号和 DNA 修复的协同过程来实现的。由于 DNA 重组功能障碍引起的原发性免疫缺陷可根据 T 细胞的存在与否分为严重联合免疫缺陷或其他情况。我们还可以将这些疾病分为对射线敏感或非对射线敏感的免疫缺陷。虽然不能触发 DNA 切割的疾病不表现出对射线的敏感性，但 DSB 反应信号或修复的功能障碍确实会导致对射线敏感的免疫缺陷。最近的研究已经开始阐明这种与 DNA DSB 相关的原发性免疫缺陷的分子发病机制的机制。
