ELEMENTS REGULATING SOMATIC HYPERMUTATION OF AN IMMUNOGLOBULIN-KAPPA GENE - CRITICAL ROLE FOR THE INTRON ENHANCER MATRIX ATTACHMENT REGION
ELEMENTS REGULATING SOMATIC HYPERMUTATION OF AN IMMUNOGLOBULIN-KAPPA GENE - CRITICAL ROLE FOR THE INTRON ENHANCER MATRIX ATTACHMENT REGION
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DOI：
10.1016/0092-8674(94)90316-6
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发表时间：
1994-04-22
期刊：
影响因子：
64.5
通讯作者：
NEUBERGER, MS
中科院分区：
文献类型：
--
作者：
BETZ, AG;MILSTEIN, C;NEUBERGER, MS
在与抗原接触后，B淋巴细胞中的免疫球蛋白基因会发生体细胞高频突变。大多数核苷酸替换发生在由V基因启动子和内含子增强子侧翼的区域。在此所描述的利用转基因小鼠进行的实验表明，Vκ启动子不包含特定信号，因为当用β - 球蛋白启动子替代它时，高频突变仍然存在。然而，发现κ内含子和κ 3'增强子区域对于完全的高频突变都是必不可少的。高频突变对这两种增强子的依赖性与杂交瘤中的转基因表达形成对比，在杂交瘤中，只有3'增强子（而非内含子增强子）是实现高mRNA水平所必需的。结果表明，完全的高频突变依赖于多种元件，其中一些元件的缺失可能会严重损害但不会完全消除这一过程。
Following encounter with antigen, the immunoglobulin genes in B lymphocytes undergo somatic hypermutation. Most nucleotide substitutions are introduced into a region flanked by the V gene promoter and intron enhancer. Experiments described here using transgenic mice revealed that the V kappa promoter does not contain specific signals since hypermutation was retained on substituting it by a beta-globin promoter. However, both the kappa intron and kappa 3' enhancer regions were found to be essential for full hypermutation. This dependence of hypermutation on both enhancers contrasts with transgene expression in hybridomas in which only the 3' enhancer (and not the intron enhancer) is necessary to achieve high mRNA levels. The results show that full hypermutation depends on multiple elements, removal of some of which may drastically impair but not totally abolish the process.