MOUSE KAPPA-LIGHT-CHAIN RECOMBINATION SIGNAL SEQUENCES MEDIATE RECOMBINATION MORE FREQUENTLY THAN DO THOSE OF LAMBDA-LIGHT CHAIN
MOUSE KAPPA-LIGHT-CHAIN RECOMBINATION SIGNAL SEQUENCES MEDIATE RECOMBINATION MORE FREQUENTLY THAN DO THOSE OF LAMBDA-LIGHT CHAIN
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DOI：
10.1073/pnas.88.23.10721
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
WU, GE
中科院分区：
文献类型：
--
作者：
RAMSDEN, DA;WU, GE
免疫球蛋白和T细胞受体基因通过位点特异性重组进行体细胞重排。已确定的信号序列（RSS）的主要靶向元素的这一过程。最近的报道表明，RSS的差异影响重组的频率，这表明RSS在B细胞库的发展中的作用。对小鼠轻链RSS的检查表明，κ-轻链RSS始终显示出比β-轻链更大程度的与共有序列的相似性。为了确定这种差异是否在天然RSS可能会影响轻链基因重排和表达的模式，我们构建了重组基板含有一个典型的小鼠kappa-RSS对和一个典型的小鼠kappa-RSS对。使用这些基板的实验表明，kappa-RSS对介导的重组在一个大大高于频率比的randa-RSS对。这一结果表明，RSS的差异可能会显着贡献的小鼠免疫球蛋白轻链重排的模式，最终导致在一个高比例的κ-轻链相对于λ。
Immunoglobulin and T-cell receptor genes are somatically rearranged by site-specific recombination. Recombination signal sequences (RSS) have been identified as the major targeting element of this process. Recent reports demonstrate that differences in RSS affect the frequency of recombination, suggesting a role for RSS in the development of the B-cell repertoire. Examination of mouse light-chain RSS indicates that kappa-light-chain RSS consistently show a greater degree of similarity to a consensus sequence than do those of lambda-light chain. To determine whether this difference in natural RSS could affect the patterns of light-chain gene rearrangement and expression, we have constructed recombination substrates containing both a typical mouse kappa-RSS pair and a typical mouse lambda-RSS pair. Experiments using these substrates demonstrate that the kappa-RSS pair mediates recombination at a vastly higher frequency than does the lambda-RSS pair. This result argues that RSS differences may contribute significantly to the patterns of mouse immunoglobulin light-chain rearrangement, ultimately resulting in a high proportion of kappa-light chain relative to lambda.