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对携带μ链免疫球蛋白转基因小鼠的独特型模拟和等位基因排斥的定量分析。

Quantitative analysis of idiotypic mimicry and allelic exclusion in mice with a mu Ig transgene.

作者信息

Rath S, Durdik J, Gerstein R M, Selsing E, Nisonoff A

机构信息

Department of Biology, Brandeis University, Waltham, MA 02254-9110.

出版信息

J Immunol. 1989 Sep 15;143(6):2074-80.

PMID:2476495
Abstract

Analysis of C57BL/6 mice (IgM allotype, Igh-6b or mu b) that carry an Ig H chain transgene of a different allotype (mu a) shows that IgM molecules of mixed allotype (mu a mu b) are present among serum antibodies. The finding was extended to hybridomas prepared from nonimmune transgenic mice, many of which also failed to exhibit allelic exclusion. The proportions of mu a and mu b secreted by individual hybridomas varied markedly, and the product of an individual hybridoma was found to be heterogeneous with respect to the allotype content of individual molecules. The ratio of mu a:mu b chains secreted by individual hybridomas was found to correlate with the number of transgene copies remaining in each hybridoma, and several hybridomas that secrete only mu b-positive molecules had apparently lost all but one copy of the transgene. An idiotype characteristic of the transgene was found to be present only in association with the transgenic (mu a) allotype, and indirect evidence strongly suggests that the idiotype was present only on mu a polypeptide chains. Thus, there is no evidence in this system for the induction of idiotypically cross-reactive endogenous molecules.

摘要

对携带不同同种异型(μa)的Ig H链转基因的C57BL/6小鼠(IgM同种异型,Igh-6b或μb)进行分析,结果显示血清抗体中存在混合同种异型(μaμb)的IgM分子。这一发现扩展到了从非免疫转基因小鼠制备的杂交瘤,其中许多也未能表现出等位基因排斥。各个杂交瘤分泌的μa和μb比例差异显著,并且发现单个杂交瘤的产物在单个分子的同种异型含量方面是异质的。发现各个杂交瘤分泌的μa:μb链比例与每个杂交瘤中剩余的转基因拷贝数相关,并且一些仅分泌μb阳性分子的杂交瘤显然除了一个转基因拷贝外其余都已丢失。发现转基因特有的独特型仅与转基因(μa)同种异型相关,并且间接证据强烈表明该独特型仅存在于μa多肽链上。因此,在这个系统中没有证据表明存在独特型交叉反应性内源性分子的诱导。

相似文献

1
Quantitative analysis of idiotypic mimicry and allelic exclusion in mice with a mu Ig transgene.对携带μ链免疫球蛋白转基因小鼠的独特型模拟和等位基因排斥的定量分析。
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引用本文的文献

1
Translocation of an antibody transgene requires AID and occurs by interchromosomal switching to all switch regions except the mu switch region.抗体转基因的易位需要 AID,并通过染色体间转换到除 mu 开关区以外的所有开关区发生。
Eur J Immunol. 2011 May;41(5):1456-64. doi: 10.1002/eji.201041077. Epub 2011 Apr 11.
2
Expression levels of B cell surface immunoglobulin regulate efficiency of allelic exclusion and size of autoreactive B-1 cell compartment.B细胞表面免疫球蛋白的表达水平调节等位基因排斥的效率和自身反应性B-1细胞区室的大小。
J Exp Med. 1999 Aug 16;190(4):461-69. doi: 10.1084/jem.190.4.461.
3
Differentiation of growth signal requirement of B lymphocyte precursor is directed by expression of immunoglobulin.
B淋巴细胞前体对生长信号需求的分化由免疫球蛋白的表达所引导。
EMBO J. 1991 Feb;10(2):337-42. doi: 10.1002/j.1460-2075.1991.tb07954.x.
4
Immunoglobulin (Ig) mu, kappa transgenic mice express transgenic idiotype on endogenously rearranged IgM and IgA molecules by secretion of chimeric molecules.免疫球蛋白(Ig)μ、κ转基因小鼠通过分泌嵌合分子,在内源性重排的IgM和IgA分子上表达转基因独特型。
J Exp Med. 1992 Oct 1;176(4):951-61. doi: 10.1084/jem.176.4.951.
5
Chromosomal position of rearranging gene segments influences allelic exclusion in transgenic mice.重排基因片段的染色体位置影响转基因小鼠中的等位基因排斥。
Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2205-8. doi: 10.1073/pnas.89.6.2205.