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免疫球蛋白κ轻链可变基因片段与连接基因片段之间的DNA经常保留在重排κ基因座的细胞中。

DNA between variable and joining gene segments of immunoglobulin kappa light chain is frequently retained in cells that rearrange the kappa locus.

作者信息

Van Ness B G, Coleclough C, Perry R P, Weigert M

出版信息

Proc Natl Acad Sci U S A. 1982 Jan;79(2):262-6. doi: 10.1073/pnas.79.2.262.

Abstract

A systematic analysis of the fate of the DNA between kappa chain variable (V kappa) and joining (J kappa) genes in cells that have rearranged kappa loci was carried out. The DNA from a variety of kappa-producing plasmacytomas, lambda-producing hybridomas, and kappa-expressing lymphocytes was digested, fractionated by size, and analyzed with two probes containing sequences 5' of J kappa. In 13 of 28 plasmacytomas examined the rearrangement of V kappa and J kappa appears to be accompanied by loss of DNA upstream of J kappa. However, in the rest of the plasmacytomas one or more upstream sequences are retained in a new context. In 9 of 12 lambda-producing hybridomas (which frequently rearrange both kappa loci) one or more upstream segments were detected. These unique fragments were probably generated by a recombination event near or at the J kappa region. The extent to which the region between V and J is maintained in kappa-expression lymphocytes was also measured. Most (76%) of the region upstream of J kappa is retained in the population, even though 68% of the kappa loci are rearranged. In order to explain how these upstream elements occur in some, but not all, cell lines, and the significant occurrence in the lymphocyte population, we propose a model in which a step in V--J joining involves mitotic recombination by unequal sister chromatid exchange.

摘要

对已重排κ基因座的细胞中κ链可变区(Vκ)和连接区(Jκ)基因之间DNA的命运进行了系统分析。从多种产生κ链的浆细胞瘤、产生λ链的杂交瘤以及表达κ链的淋巴细胞中提取DNA,进行酶切、按大小分级分离,并用两个含有Jκ上游序列的探针进行分析。在检测的28个浆细胞瘤中,有13个Vκ和Jκ的重排似乎伴随着Jκ上游DNA的缺失。然而,在其余的浆细胞瘤中,一个或多个上游序列在新的环境中得以保留。在12个产生λ链的杂交瘤(其κ基因座经常发生重排)中有9个检测到一个或多个上游片段。这些独特的片段可能是由Jκ区域附近或Jκ区域发生的重组事件产生的。还测定了在表达κ链的淋巴细胞中V和J之间区域的保留程度。尽管68%的κ基因座发生了重排,但Jκ上游区域的大部分(76%)在细胞群体中得以保留。为了解释这些上游元件如何在一些而非所有细胞系中出现,以及在淋巴细胞群体中的显著出现情况,我们提出了一个模型,其中V-J连接的一个步骤涉及通过不等姐妹染色单体交换进行的有丝分裂重组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/2ebef9707cef/pnas00441-0063-a.jpg

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