Clustered Mutations at the Murine and Human IgH Locus Exhibit Significant Linkage Consistent with Templated Mutagenesis
Clustered Mutations at the Murine and Human IgH Locus Exhibit Significant Linkage Consistent with Templated Mutagenesis
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DOI：
10.4049/jimmunol.1801615
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发表时间：
2019-09-01
影响因子：
4.4
通讯作者：
Jacob, Joshy
中科院分区：
文献类型：
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作者：
Dale, Gordon A.;Wilkins, Daniel J.;Jacob, Joshy
体细胞超突变在Ag特异性B细胞中产生大量Ab突变体，从中选择高亲和力突变体。鸡、羊和兔通过基因转换使用非模板点突变和模板突变来使其表达的IG基因座多样化，而小鼠和人类仅依赖于非模板体细胞点突变。在这项研究中，我们证明，除了非模板点突变，模板诱变容易发生在小鼠和人的IG基因座。我们提供了两条不同的证据线，这些证据不能用Neuberger体细胞超突变模型来解释：1）在多个数据集中，个体突变之间存在显着的连锁不平衡，特别是在紧密突变之间，2）在这些突变中，
Somatic hypermutation generates a myriad of Ab mutants in Ag-specific B cells, from which high-affinity mutants are selected. Chickens, sheep, and rabbits use nontemplated point mutations and templated mutations via gene conversion to diversify their expressed Ig loci, whereas mice and humans rely solely on untemplated somatic point mutations. In this study, we demonstrate that, in addition to untemplated point mutations, templated mutagenesis readily occurs at the murine and human Ig loci. We provide two distinct lines of evidence that are not explained by the Neuberger model of somatic hypermutation: 1) across multiple data sets there is significant linkage disequilibrium between individual mutations, especially among close mutations, and 2) among those mutations, those