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 1

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 1
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由激活诱导的胞苷脱氨酶缺陷引起的免疫球蛋白类别开关重组的阻断发生在开关 μ 区 1 中 DNA 双链断裂的产生之前

DOI:
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发表时间:
2003
影响因子:
4.4
通讯作者:
A. Durandy
A. Durandy
中科院分区:
医学2区
文献类型:
--
作者:
Nadia Catalan;F. Selz;K. Imai;P. Revy;A. Fischer;A. Durandy

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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 Sμ 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.
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