A uniform deleting element mediates the loss of κ genes in human B cells
A uniform deleting element mediates the loss of κ genes in human B cells
复制标题
统一删除元件介导人类 B 细胞中 κ 基因的丢失
作者：
K. Siminovitch;A. Bakhshi;P. Goldman;S. Korsmeyer
人免疫球蛋白轻链基因在前B细胞发育期间以有序方式重排，使得重排通常发生在λ基因之前的κ基因中（参考文献1，2）。这个有序的过程包括在λ重组1 -4之前的恒定κ（Cκ）基因和κ增强子序列的意外缺失，并且在75%的研究病例中，这种缺失重组的位点位于连接（Jκ）片段的3′端。我们现在已经在三个不同的等位基因上鉴定了引起这一事件的重组元件，并发现它们是相同的。该κ缺失元件与位于Jκ-Cκ内含子中的回文信号（CACAGTG）位点特异性重组。其他人类B细胞中Cκ基因的所有丢失都是由该决定子介导的，包括该元件与Jκ 5′端序列重组的25%的情况。相比之下，κ-缺失元件在所有成功产生κ的等位基因上保持其种系形式。此外，κ缺失是进化保守事件，因为κ缺失元件似乎是鼠RS序列的人类同源物5。我们的研究结果表明，该元素可能有助于确保轻链的同种型和等位基因排斥，并可能参与人类轻链基因的有序使用。
Human immunoglobulin light-chain genes become rearranged in an ordered fashion during pre-B-cell development such that rearrangement generally occurs in κ genes before λ genes (refs 1,2). This ordered process includes an unanticipated deletion of the constant κ (Cκ) gene and κ enhancer sequence which precedes λ rearrangement1–4, and the site of this deletional recombination was located 3′ to the joining ( Jκ) segments in 75% of cases studied. We have now characterized the recombinational element responsible for this event on three separate alleles and found them to be identical. This κ-deleting element recombined site-specifically with a palindromic signal (CACAGTG) located in the Jκ–Cκ intron. All losses of Cκ genes in other human B cells were mediated by this determinant, including the 25% of instances when this element recombined with sequences 5′ to Jκ. In contrast, the κ-deleting element remained in its germline form on all successful κ-producing alleles. Moreover, κ loss is an evolutionary conserved event, as the κ-deleting element appears to be the human homologue of the murine RS sequence5. Our results suggest that this element may help ensure isotypic and allelic exclusion of light chains and may be involved in the ordered use of human light-chain genes.
登录
查看更多内容
影响因子：
56.9
作者：
EPHRUSSI, A;CHURCH, GM;GILBERT, W
通讯作者：
GILBERT, W
影响因子：
20.3
作者：
R. Stong;S. Korsmeyer;J. Parkin;D. Arthur;J. Kersey
通讯作者：
R. Stong;S. Korsmeyer;J. Parkin;D. Arthur;J. Kersey
非T细胞急性淋巴细胞白血病的B细胞起源。
DOI：
10.1172/jci111428
发表时间：
1984
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Nadler,LM;Korsmeyer,SJ;Anderson,KC;Boyd,AW;Slaughenhoupt,B;Park,E;Jensen,J;Coral,F;Mayer,RJ;Sallan,SE
通讯作者：
Sallan,SE
免疫球蛋白重链增强剂需要一种或多种组织特异性因子。
DOI：
10.1126/science.3917575
发表时间：
1985
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Mercola,M;Goverman,J;Mirell,C;Calame,K
通讯作者：
Calame,K