The block in immunoglobulin class switch recombination caused by activation-induced cytidine deaminase deficiency occurs prior to the generation of DNA double strand breaks in switch μ region
The block in immunoglobulin class switch recombination caused by activation-induced cytidine deaminase deficiency occurs prior to the generation of DNA double strand breaks in switch μ region
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DOI：
10.4049/jimmunol.171.5.2504
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发表时间：
2003-09-01
影响因子：
4.4
通讯作者：
Durandy, A
中科院分区：
文献类型：
--
作者：
Catalan, N;Selz, F;Durandy, A
生发中心抗体谱系的亲和力成熟导致选择具有选定重链恒定区的高亲和力抗体。AB成熟涉及Ig基因的两个修饰，即体细胞超突变和类开关重组。这两个过程的机制还没有完全被理解。激活诱导型胞苷脱氨酶(AID)缺陷患者和小鼠的体细胞高突变和类开关重组缺陷表型表明，这两个过程都需要AID分子。体细胞DNA修饰需要DNA断裂，这至少对于类切换重组来说，会导致dsDNA断裂。通过连接介导的聚合酶链式反应发现，在AID缺陷的B细胞中，类开关重组引起的SMU转换区的dsDNA断裂的频率低于AID熟练的B细胞，从而表明AID在DNA断裂诱导的上游起作用。
Affinity maturation of the Ab repertoire in germinal centers leads to the selection of high affinity Abs with selected heavy chain constant regions. Ab maturation involves two modifications of the Ig genes, i.e., somatic hypermutation and class switch recombination. The mechanisms of these two processes are not fully understood. As shown by the somatic hypermutation and class switch recombination-deficient phenotype of activation-induced cytidine deaminase (AID)-deficient patients (hyperIgM type 2 syndrome) and mice, both processes require the AID molecule. Somatic DNA modifications require DNA breaks, which, at least for class switch recombination, lead to dsDNA breaks. By using a ligation-mediated PCR, it was found that class switch recombination-induced dsDNA breaks in Smu switch regions were less frequent in AID-deficient B cells than in AID-proficient B cells, thus indicating that AID acts upstream of DNA break induction.