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免疫球蛋白基因“残留”DNA——对抗体基因重组的影响

Immunoglobulin gene 'remnant' DNA--implications for antibody gene recombination.

作者信息

Selsing E, Voss J, Storb U

出版信息

Nucleic Acids Res. 1984 May 25;12(10):4229-46. doi: 10.1093/nar/12.10.4229.

DOI:10.1093/nar/12.10.4229
PMID:6328416
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC318828/
Abstract

Many immunoglobulin (Ig)-producing cells retain the DNA that separates Ig variable (V) and constant (C) region genes in the germline. This "remnant" DNA must be moved during the recombination process that joins V and C genes via a joining (J) segment. We have analyzed remnant DNAs in several Ig-producing cell lines. The nucleotide sequences of kappa (kappa) light chain remnant DNAs indicate close relationships to V-J joining. We find fused V kappa and J kappa recognition sequences in five remnant DNAs, suggesting reciprocal relationships to the fused V kappa and J kappa segments produced by V-J joining. However, of sixteen plasmacytoma remnant DNAs analyzed, all involve only recombination with J kappa l. Thus, in most cell lines, remnant DNAs are not directly reciprocal to recombined kappa-genes. On the other hand, our analyses of some myelomas do indicate indirect relationships between remnant DNAs and kappa-genes. Our results suggest that multiple steps of DNA recombination occur during Ig-gene rearrangement. Because remnant DNA joining sites do not exhibit the flexibility that has been observed in Ig-gene V-J joining, our findings also suggest that the joining mechanism may involve endonuclease, exonuclease and ligase activities.

摘要

许多产生免疫球蛋白（Ig）的细胞保留着种系中分隔Ig可变（V）区和恒定（C）区基因的DNA。在通过连接（J）片段连接V基因和C基因的重组过程中，这种“残留”DNA必须移动。我们分析了几种产生Ig的细胞系中的残留DNA。κ轻链残留DNA的核苷酸序列表明其与V-J连接密切相关。我们在五个残留DNA中发现了融合的Vκ和Jκ识别序列，这表明其与V-J连接产生的融合Vκ和Jκ片段存在相互关系。然而，在分析的16个浆细胞瘤残留DNA中，所有DNA都仅涉及与Jκ1的重组。因此，在大多数细胞系中，残留DNA与重组的κ基因并非直接相互对应。另一方面，我们对一些骨髓瘤的分析确实表明残留DNA与κ基因之间存在间接关系。我们的结果表明，Ig基因重排过程中发生了多个DNA重组步骤。由于残留DNA连接位点未表现出Ig基因V-J连接中所观察到的灵活性，我们的发现还表明连接机制可能涉及内切核酸酶、外切核酸酶和连接酶活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/16dae54ae20d/nar00328-0195-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/1f235f847a61/nar00328-0188-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/068bbd517451/nar00328-0192-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/84b7bed6dd71/nar00328-0193-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/16dae54ae20d/nar00328-0195-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/1f235f847a61/nar00328-0188-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/068bbd517451/nar00328-0192-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/84b7bed6dd71/nar00328-0193-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5839/318828/16dae54ae20d/nar00328-0195-a.jpg

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Sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene.靠近免疫球蛋白κ恒定区基因编码的五个潜在重组位点的序列。
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Double recombination of a single immunoglobulin kappa-chain allele: implications for the mechanism of rearrangement.单个免疫球蛋白κ链等位基因的双重重组：对重排机制的影响
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Organization and sequences of the variable, joining and constant region genes of the human T-cell receptor alpha-chain.人类T细胞受体α链可变区、连接区和恒定区基因的组织与序列
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Annu Rev Immunol. 2000;18:19-51. doi: 10.1146/annurev.immunol.18.1.19.
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Junctional diversity in signal joints from T cell receptor beta and delta loci via terminal deoxynucleotidyl transferase and exonucleolytic activity.通过末端脱氧核苷酸转移酶和核酸外切酶活性，T细胞受体β和δ基因座信号接头中的连接多样性。

本文引用的文献

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Anti-phosphocholine hybridoma antibodies. II. Functional analysis of binding sites within three antibody families.抗磷酸胆碱杂交瘤抗体。II. 三个抗体家族内结合位点的功能分析。
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Mapping of immunoglobulin variable region genes: relationship to the 'deletion' model of immunoglobulin gene rearrangement.免疫球蛋白可变区基因的图谱绘制：与免疫球蛋白基因重排的“缺失”模型的关系
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Somatic mutation of immunoglobulin light-chain variable-region genes.免疫球蛋白轻链可变区基因的体细胞突变
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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.
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Human immunoglobulin kappa light-chain genes are deleted or rearranged in lambda-producing B cells.人类免疫球蛋白κ轻链基因在产生λ链的B细胞中发生缺失或重排。
Nature. 1981 Apr 2;290(5805):368-72. doi: 10.1038/290368a0.
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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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