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IgH增强子的缺失不会降低杂交瘤IgD类转换变体的免疫球蛋白重链产量。

Deletion of the IgH enhancer does not reduce immunoglobulin heavy chain production of a hybridoma IgD class switch variant.

作者信息

Klein S, Sablitzky F, Radbruch A

出版信息

EMBO J. 1984 Nov;3(11):2473-6. doi: 10.1002/j.1460-2075.1984.tb02158.x.

DOI:10.1002/j.1460-2075.1984.tb02158.x
PMID:6096124
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC557714/
Abstract

Immunoglobulin (Ig) gene promotors are active only in cells of the B-lymphocyte lineage. Transfection experiments have shown that this is due in part to tissue specific 'activating' DNA sequences, so called enhancers. It is not entirely clear whether these sequences are necessary for initial activation or also for maintenance of transcription of a gene. We describe here the isolation and characterisation of a mouse hybridoma cell line that has deleted in vitro the 'activating' sequence from the active IgH locus, the only IgH locus it contains. Nevertheless, Ig heavy chain production of the variant cell is not impaired and remains comparable with that of other hybridoma cells. Therefore, a high rate of Ig heavy chain production in antibody-producing cells is either independent of any sequences enhancing transcription or else these can easily be replaced by other DNA sequences with a similar function that have been moved into the vicinity of the V region.

摘要

免疫球蛋白(Ig)基因启动子仅在B淋巴细胞谱系的细胞中具有活性。转染实验表明,这部分归因于组织特异性的“激活”DNA序列,即所谓的增强子。目前尚不完全清楚这些序列对于基因的初始激活是否必要,还是对于基因转录的维持也同样必要。我们在此描述了一种小鼠杂交瘤细胞系的分离和特性鉴定,该细胞系在体外已从其唯一包含的活性IgH基因座中删除了“激活”序列。然而,变异细胞的Ig重链产生并未受损,并且与其他杂交瘤细胞相当。因此,抗体产生细胞中Ig重链的高产量要么独立于任何增强转录的序列,要么这些序列可以很容易地被具有类似功能且已转移到V区附近的其他DNA序列所取代。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/557714/1cb804e59fb1/emboj00315-0034-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/557714/d081cb9cd309/emboj00315-0033-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/557714/8637750a864e/emboj00315-0034-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/557714/1cb804e59fb1/emboj00315-0034-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/557714/d081cb9cd309/emboj00315-0033-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/557714/8637750a864e/emboj00315-0034-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a112/557714/1cb804e59fb1/emboj00315-0034-b.jpg

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1
Deletion of the IgH enhancer does not reduce immunoglobulin heavy chain production of a hybridoma IgD class switch variant.IgH增强子的缺失不会降低杂交瘤IgD类转换变体的免疫球蛋白重链产量。
EMBO J. 1984 Nov;3(11):2473-6. doi: 10.1002/j.1460-2075.1984.tb02158.x.
2
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Nucleotide sequences of immunoglobulin mu heavy chain deletion mutants.免疫球蛋白μ重链缺失突变体的核苷酸序列。
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Genomic deletion of the whole IgH 3' regulatory region (hs3a, hs1,2, hs3b, and hs4) dramatically affects class switch recombination and Ig secretion to all isotypes.基因组缺失整个 IgH3'调控区(hs3a、hs1、2、hs3b 和 hs4)显著影响所有同种型的类别转换重组和 Ig 分泌。
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Use of a simple, general targeting vector for replacing the DNA of the heavy chain constant region in mouse hybridoma cells.使用一种简单的通用靶向载体替换小鼠杂交瘤细胞中重链恒定区的DNA。
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The in vivo generation of murine IgD-secreting cells is accompanied by deletion of the C mu gene and occasional deletion of the gene for the C delta 1 domain.小鼠IgD分泌细胞的体内生成伴随着Cμ基因的缺失以及Cδ1结构域基因的偶尔缺失。
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The immunoglobulin heavy-chain B-lymphocyte enhancer efficiently stimulates transcription in non-lymphoid cells.免疫球蛋白重链B淋巴细胞增强子可有效刺激非淋巴细胞中的转录。
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Nuclear factors binding to the human immunoglobulin heavy-chain gene enhancer.与人类免疫球蛋白重链基因增强子结合的核因子。
Nucleic Acids Res. 1987 Apr 10;15(7):2851-69. doi: 10.1093/nar/15.7.2851.
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Evidence for transient requirement of the IgH enhancer.免疫球蛋白重链增强子短暂需求的证据。
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Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells.转染至淋巴细胞中的免疫球蛋白重链基因的表达与调控
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Immunoglobulin V region variants in hybridoma cells. II. Recombination between V genes.杂交瘤细胞中的免疫球蛋白V区变体。II. V基因之间的重组
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Cross-reactivity of the NPa and NPb idiotypic responses of BALB/c and C57BL/6 mice to (4-hydroxy-3-nitrophenyl)acetyl (NP).
Two forms of loops generate the chromatin conformation of the immunoglobulin heavy-chain gene locus.
两种环式结构生成免疫球蛋白重链基因座的染色质构象。
Cell. 2011 Oct 14;147(2):332-43. doi: 10.1016/j.cell.2011.08.049. Epub 2011 Oct 6.
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Transcription of a productively rearranged Ig VDJC alpha does not require the presence of HS4 in the IgH 3' regulatory region.有功能重排的Ig VDJCα的转录并不需要IgH 3'调控区中HS4的存在。
J Immunol. 2007 May 15;178(10):6297-306. doi: 10.4049/jimmunol.178.10.6297.
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Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions.在内源免疫球蛋白重链基因座的重组和转录过程中,在缺乏基质附着区域的情况下,由免疫球蛋白重链内含子增强子核心区域发挥作用。
Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1526-31. doi: 10.1073/pnas.96.4.1526.
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Enhancer complexes located downstream of both human immunoglobulin Calpha genes.位于两个人类免疫球蛋白Cα基因下游的增强子复合体。
J Exp Med. 1997 Sep 15;186(6):845-58. doi: 10.1084/jem.186.6.845.
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Expression of the (recombinant) endogenous immunoglobulin heavy-chain locus requires the intronic matrix attachment regions.(重组)内源性免疫球蛋白重链基因座的表达需要内含子基质附着区域。
Mol Cell Biol. 1997 May;17(5):2658-68. doi: 10.1128/MCB.17.5.2658.
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An element in the endogenous IgH locus stimulates gene targeting in hybridoma cells.内源性免疫球蛋白重链基因座中的一个元件可刺激杂交瘤细胞中的基因靶向作用。
Nucleic Acids Res. 1996 Apr 15;24(8):1525-30. doi: 10.1093/nar/24.8.1525.
10
Immunoglobulin gene transcription ceases upon deletion of a distant enhancer.免疫球蛋白基因转录在一个远距离增强子缺失后停止。
EMBO J. 1995 Dec 15;14(24):6229-38. doi: 10.1002/j.1460-2075.1995.tb00313.x.
BALB/c和C57BL/6小鼠针对(4-羟基-3-硝基苯基)乙酰基(NP)的NPa和NPb独特型反应的交叉反应性。
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Isolation of a cloned cell line expressing variant H-2Kk using fluorescence-activated cell sorting.利用荧光激活细胞分选技术分离表达变异型H-2Kk的克隆细胞系。
Nature. 1981 Jan 1;289(5793):66-8. doi: 10.1038/289066a0.
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Mouse immunoglobulin D: messenger RNA and genomic DNA sequences.小鼠免疫球蛋白D:信使核糖核酸和基因组脱氧核糖核酸序列。
Science. 1980 Sep 19;209(4463):1353-60. doi: 10.1126/science.6968091.
6
Switch from hapten-specific immunoglobulin M to immunoglobulin D secretion in a hybrid mouse cell line.在一个杂交小鼠细胞系中,从半抗原特异性免疫球蛋白M分泌转换为免疫球蛋白D分泌。
Proc Natl Acad Sci U S A. 1981 Feb;78(2):1138-42. doi: 10.1073/pnas.78.2.1138.
7
Utilization of the biotin/avidin system to amplify the sensitivity of the enzyme-linked immunosorbent assay (ELISA).利用生物素/抗生物素蛋白系统提高酶联免疫吸附测定(ELISA)的灵敏度。
J Immunol Methods. 1983 Feb 11;56(3):329-39. doi: 10.1016/s0022-1759(83)80022-2.
8
Organization of the constant-region gene family of the mouse immunoglobulin heavy chain.小鼠免疫球蛋白重链恒定区基因家族的组织
Cell. 1982 Mar;28(3):499-506. doi: 10.1016/0092-8674(82)90204-5.
9
Heavy chain variable region contribution to the NPb family of antibodies: somatic mutation evident in a gamma 2a variable region.重链可变区对NPb抗体家族的贡献:γ2a可变区中明显的体细胞突变。
Cell. 1981 Jun;24(3):625-37. doi: 10.1016/0092-8674(81)90089-1.
10
Mouse immunoglobulin D: construction and characterization of a cloned delta chain cDNA.小鼠免疫球蛋白D:克隆的δ链cDNA的构建与表征
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7405-9. doi: 10.1073/pnas.77.12.7405.