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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.

DOI:10.1073/pnas.79.2.262
PMID:6804938
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC345706/
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/9c43/345706/8e120ed2fba0/pnas00441-0064-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/2ebef9707cef/pnas00441-0063-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/adc583904705/pnas00441-0063-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/b0253c2169bb/pnas00441-0063-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/8e120ed2fba0/pnas00441-0064-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/2ebef9707cef/pnas00441-0063-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/adc583904705/pnas00441-0063-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/b0253c2169bb/pnas00441-0063-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c43/345706/8e120ed2fba0/pnas00441-0064-a.jpg

相似文献

1
DNA between variable and joining gene segments of immunoglobulin kappa light chain is frequently retained in cells that rearrange the kappa locus.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。
Proc Natl Acad Sci U S A. 1982 Jan;79(2):262-6. doi: 10.1073/pnas.79.2.262.
2
A novel type of aberrant recombination in immunoglobulin genes and its implications for V-J joining mechanism.免疫球蛋白基因中一种新型的异常重组及其对V-J连接机制的影响。
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The joining of V and J gene segments creates antibody diversity.V基因片段和J基因片段的连接产生抗体多样性。
Nature. 1980 Jan 31;283(5746):497-9. doi: 10.1038/283497a0.
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Immunoglobulin V/J recombination is accompanied by deletion of joining site and variable region segments.免疫球蛋白V/J重组伴随着连接位点和可变区片段的缺失。
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Methylation status and DNase I sensitivity of immunoglobulin genes: changes associated with rearrangement.免疫球蛋白基因的甲基化状态和DNase I敏感性:与重排相关的变化
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7
Aberrant rearrangement of the kappa light-chain locus involving the heavy-chain locus and chromosome 15 in a mouse plasmacytoma.一只小鼠浆细胞瘤中κ轻链基因座的异常重排,涉及重链基因座和15号染色体。
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Recombined flanks of the variable and joining segments of immunoglobulin genes.免疫球蛋白基因可变区和连接区的重组侧翼序列。
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Plasmacytomas with more than one immunoglobulin kappa mRNA: implications for allelic exclusion.具有不止一种免疫球蛋白κ mRNA 的浆细胞瘤:对等位基因排斥的影响
Proc Natl Acad Sci U S A. 1981 Sep;78(9):5812-6. doi: 10.1073/pnas.78.9.5812.

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2
Efficient AID targeting of switch regions is not sufficient for optimal class switch recombination.高效的 AID 靶向开关区对于最佳类别转换重组并不足够。
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本文引用的文献

1
Reorganization and expression of immunoglobulin genes: status of allelic elements.免疫球蛋白基因的重组与表达:等位基因元件的状态
Cold Spring Harb Symp Quant Biol. 1981;45 Pt 2:925-33. doi: 10.1101/sqb.1981.045.01.109.
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Structure of a rearranged gamma 1 chain gene and its implication to immunoglobulin class-switch mechanism.重排的γ1链基因结构及其对免疫球蛋白类别转换机制的影响。
Proc Natl Acad Sci U S A. 1981 Apr;78(4):2437-41. doi: 10.1073/pnas.78.4.2437.
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Identification and nucleotide sequence of a diversity DNA segment (D) of immunoglobulin heavy-chain genes.
YY1 控制 Igκ 受体库和 B 细胞发育,并与凝聚素一起定位于 Igκ 基因座上。
EMBO J. 2013 Apr 17;32(8):1168-82. doi: 10.1038/emboj.2013.66. Epub 2013 Mar 26.
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Receptor editing in self-reactive bone marrow B cells. The Journal of Experimental Medicine. 1993. 177: 1009-1020.自身反应性骨髓 B 细胞中的受体编辑。实验医学杂志。1993 年。177: 1009-1020.
J Immunol. 2011 Feb 1;186(3):1313-24.
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Revising B cell receptors.修订B细胞受体。
J Exp Med. 2000 Jun 5;191(11):1813-7. doi: 10.1084/jem.191.11.1813.
6
Restricted immunoglobulin variable region (Ig V) gene expression accompanies secondary rearrangements of light chain Ig V genes in mouse plasmacytomas.在小鼠浆细胞瘤中,受限的免疫球蛋白可变区(Ig V)基因表达伴随着轻链Ig V基因的二次重排。
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Somatic diversification of antibody responses.抗体应答的体细胞多样化
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Receptor editing in self-reactive bone marrow B cells.自身反应性骨髓B细胞中的受体编辑
J Exp Med. 1993 Apr 1;177(4):1009-20. doi: 10.1084/jem.177.4.1009.
9
Addition of constitutive c-myc expression to Abelson murine leukemia virus changes the phenotype of the cells transformed by the virus from pre-B-cell lymphomas to plasmacytomas.将组成型c-myc表达添加到艾贝尔森鼠白血病病毒中,会使该病毒转化的细胞表型从前B细胞淋巴瘤转变为浆细胞瘤。
Mol Cell Biol. 1993 Apr;13(4):2578-85. doi: 10.1128/mcb.13.4.2578-2585.1993.
10
Elements in the immunoglobulin heavy-chain enhancer directly regulate simian virus 40 ori-dependent DNA replication.免疫球蛋白重链增强子中的元件直接调控猿猴病毒40 ori依赖性DNA复制。
Mol Cell Biol. 1993 Sep;13(9):5629-36. doi: 10.1128/mcb.13.9.5629-5636.1993.
免疫球蛋白重链基因多样性DNA片段(D)的鉴定及核苷酸序列
Nature. 1981 Apr 16;290(5807):562-5. doi: 10.1038/290562a0.
4
Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression.异常重排对免疫球蛋白基因表达的等位基因排斥有显著贡献。
Nature. 1981 Apr 2;290(5805):372-8. doi: 10.1038/290372a0.
5
Immunoglobulin V/J recombination is accompanied by deletion of joining site and variable region segments.免疫球蛋白V/J重组伴随着连接位点和可变区片段的缺失。
Proc Natl Acad Sci U S A. 1980 Oct;77(10):6022-6. doi: 10.1073/pnas.77.10.6022.
6
Variation in the crossover point of kappa immunoglobulin gene V-J recombination: evidence from a cryptic gene.κ免疫球蛋白基因V-J重组交叉点的变异:来自一个隐蔽基因的证据。
Cell. 1980 Oct;21(3):793-9. doi: 10.1016/0092-8674(80)90442-0.
7
An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH.免疫球蛋白重链可变区基因由三段DNA片段组成:VH、D和JH。
Cell. 1980 Apr;19(4):981-92. doi: 10.1016/0092-8674(80)90089-6.
8
Transcription of mouse kappa chain genes: implications for allelic exclusion.小鼠κ链基因的转录:对等位基因排斥的影响。
Proc Natl Acad Sci U S A. 1980 Apr;77(4):1937-41. doi: 10.1073/pnas.77.4.1937.
9
A rearranged DNA sequence possibly related to the translocation of immunoglobulin gene segments.一个可能与免疫球蛋白基因片段易位相关的重排DNA序列。
Nucleic Acids Res. 1980 Apr 25;8(8):1709-20. doi: 10.1093/nar/8.8.1709.
10
Association of allotypic specificities of group a with allotypic specificities A11 and A12 in rabbit immunoglobulin.兔免疫球蛋白中a组同种异型特异性与A11和A12同种异型特异性的关联
Biochemistry. 1970 Apr 28;9(9):2028-32. doi: 10.1021/bi00811a026.