The Ig kappa 3' enhancer influences the ratio of Ig kappa versus Ig lambda B lymphocytes
The Ig kappa 3' enhancer influences the ratio of Ig kappa versus Ig lambda B lymphocytes
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DOI：
10.1016/s1074-7613(00)80319-2
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发表时间：
1996-09-01
期刊：
影响因子：
32.4
通讯作者：
Alt, FW
中科院分区：
文献类型：
--
作者：
Gorman, JR;vanderStoep, N;Alt, FW
我们产生了具有种系突变的小鼠，其中位于免疫球蛋白kappa轻链基因（3e (kappa)） 9 kb 3'的增强子元件被单个loxP位点（3e (kappa)Delta）或新霉素耐药基因（3e (kappa)N）取代。3e (kappa) δ突变纯合的小鼠表达kappa的B细胞数量大幅减少，表达lambda的B细胞数量增加，同时kappa基因重排减少。在这些突变小鼠中，kappa在静止B细胞中的表达减少，但在激活B细胞中表达正常。纯合的3e (kappa)N突变导致相似但更明显的表型。这两种突变都是顺式的。这些研究表明3e （kappa）对于建立正常的kappa/lambda比率至关重要，但对于kappa基因重排或活化B细胞中正常的kappa表达并不是绝对必要的。这些研究还表明存在与3e （kappa）元件具有重叠功能的其他调节元件。
We generated mice harboring germline mutations in which the enhancer element located 9 kb 3' of the immunoglobulin kappa light chain gene (3'E(kappa)) was replaced either by a single loxP site (3'E(kappa)Delta) or by a neomycin resistance gene (3'E(kappa)N). Mice homozygous for the 3'E(kappa)Delta mutation had substantially reduced numbers of kappa-expressing B cells and increased numbers of lambda-expressing B cells accompanied by decreased kappa versus lambda gene rearrangement. In these mutant mice, kappa expression was reduced in resting B cells, but was normal in activated B cells. The homozygous 3'E(kappa)N mutation resulted in a similar but more pronounced phenotype. Both mutations acted in cis. These studies show that the 3'E(kappa) is critical for establishing the normal kappa/lambda ratio, but is not absolutely essential for kappa gene rearrangement or, surprisingly, for normal kappa expression in activated B cells. These studies also imply the existence of additional regulatory elements that have overlapping function with the 3'E(kappa) element.