Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication.
Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication.
复制标题
免疫球蛋白转基因的突变模式与体细胞超突变模型兼容，其中突变体的靶向与 DNA 复制的方向相关。
DOI：
10.1002/j.1460-2075.1991.tb05011.x
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
Storb,U
中科院分区：
文献类型：
--
作者：
Rogerson,B;HackettJr,J;Peters,A;Haasch,D;Storb,U
我们先前已经证明，在两个独立的转基因小鼠系中，B淋巴细胞特异性体细胞突变被引入到免疫球蛋白kappa转基因基因的可变区。这些突变的频率、分布和性质强烈表明，它们是体细胞超突变过程的结果，这在一定程度上是免疫反应过程中亲和力成熟的原因。出乎意料的是，在这些多拷贝转基因品系中，许多转基因拷贝没有显示出体细胞突变的证据。这一悖论是通过确定几个B细胞杂交瘤中每个转基因拷贝的序列来解决的，这些杂交瘤来自携带三个拷贝的kappa转基因的小鼠品系。研究发现，同一小鼠不同B细胞的体细胞超突变过程优先针对一个转基因拷贝，而不是相同的转基因拷贝。我们提出了一个基于这种靶向模式的模型，该模型将体细胞超突变与Ig基因相对于DNA复制方向的方向联系起来。
We have previously demonstrated that B lymphocyte specific somatic mutations are introduced into the variable regions of immunoglobulin kappa transgenes in two independent transgenic mouse lines. The frequency, distribution and nature of these mutations strongly suggest that they arose as a result of the process of somatic hypermutation, which is responsible, in part, for affinity maturation during an immune response. Unexpectedly, in these multiple copy transgenic lines, many of the transgene copies showed no evidence of somatic mutation. This paradox was addressed by determining the sequence of each transgene copy in several B cell hybridomas derived from a mouse line carrying three copies of the kappa transgene. It was found that the somatic hypermutation process in different B cells from the same mouse preferentially targets one, but not the same, transgene copy. We present a model, based on the pattern of this targeting, which links somatic hypermutation to the orientation of the Ig gene relative to the direction of DNA replication.