Defects of class-switch recombination
Defects of class-switch recombination
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DOI：
10.1016/j.jaci.2006.01.043
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发表时间：
2006-04-01
影响因子：
14.2
通讯作者：
Durandy, A
中科院分区：
文献类型：
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作者：
Notarangelo, LD;Lanzi, G;Durandy, A
二抗库的形成是通过类转换重组（CSR）和体细胞超突变（SHM）产生的，前者用其他同型替代IgM，后者允许产生高亲和力抗体。然而，这些重要过程背后的分子机制长期以来一直不清楚。高igm免疫缺陷包括一组与SHM缺陷可变相关的CSR基因异质缺陷。对这些患者的研究使我们认识到t细胞- b细胞相互作用（导致cd40介导的信号传导）和内在的b细胞机制都参与了CSR和SHM。阐明这些疾病背后的分子缺陷对于更好地理解Ig多样化的分子基础至关重要，并为定义这些疾病的临床谱和促进更准确的诊断和治疗方法提供了机会。
Shaping of the secondary antibody repertoire is generated by means of class-switch recombination (CSR), which replaces IgM with other isotypes, and somatic hypermutation (SHM), which allows production of high-affinity antibodies. However, the molecular mechanisms underlying these important processes have long remained obscure. Immunodeficiency with hyper-IgM comprises a group of genetically heterogeneous defects of CSR variably associated with defects of SHM. The study of these patients has allowed us to recognize that both T-cell-B-cell interaction (resulting in CD40-mediated signaling) and intrinsic B-cell mechanisms are involved in CSR and SHM. Elucidation of the molecular defects underlying these disorders has been essential to better understand the molecular basis of Ig diversification and has offered the opportunity to define the clinical spectrum of these diseases and to prompt more accurate diagnostic and therapeutic approaches.