TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line
TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line
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DOI：
10.1016/s1074-7613(00)80651-2
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发表时间：
1998-12-01
期刊：
影响因子：
32.4
通讯作者：
Neuberger, MS
中科院分区：
文献类型：
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作者：
Sale, JE;Neuberger, MS
为了寻找体细胞超突变的体外模型，我们发现了一种表达igm的伯基特淋巴瘤系，在培养过程中，其免疫球蛋白V结构域的组成性多样性很高。与在体内一样，突变主要是核苷酸取代，其取代模式揭示了人类超突变程序的一个组成部分，优先针对G/C残基。这些替换通常会产生具有igm丢失变体的终止密码子，这种变体也会由V结构域特定的删除和复制产生。然而，在表达末端脱氧核苷酸转移酶的转染物中，许多igm缺失变体通过短时间的非模板核苷酸插入到V（而不是C）结构域而产生。因此，抗体超突变可能伴随着分散在突变区域内的DNA链断裂。
Searching for an in vitro model for somatic hypermutation, we have identified an IgM-expressing Burkitt lymphoma line that constitutively diversifies its immunoglobulin V domain at high rate during culture. As in in vivo, the mutations are largely nucleotide substitutions with the pattern of substitutions revealing a component of the human hypermutation program that is preferentially targeted to G/C residues. The substitutions frequently create stop codons with IgM-loss variants also being generated by V domain-specific deletions and duplications. However, in transfectants expressing terminal deoxynucleotidyl transferase, many IgM-loss variants additionally arise through short nontemplated nucleotide insertions into the V (but not C) domain. Thus, antibody hypermutation is likely accompanied by DNA strand breaks scattered within the mutation domain.