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免疫球蛋白重链基因座对VK1GAC轻链表达的影响。

Influence of the immunoglobulin heavy chain locus on expression of the VK1GAC light chain.

作者信息

Fulton R J, Davie J M

出版信息

J Immunol. 1984 Jul;133(1):465-70.

PMID:6427345
Abstract

The VK1GAC light chain represents the dominant V kappa structure employed in the antibody response of A/J mice to streptococcal group A carbohydrate ( GAC ). Two anti-idiotypic antisera, anti- Id5 and anti- Id20 , with specificity for the VK1GAC light chain were used to examine anti- GAC antibody responses in a series of inbred mouse strains that differ at the heavy chain constant region ( IgCH ) allotype locus. Both idiotypes were expressed in normal and immune sera from mice of most IgCH allotypes, except IgCHb (C57BL/6J) and IgCHf (CE/J). C57BL/6J mice expressed Id5 , but not Id20 , whereas CE/J mice did not express either idiotype. Testing of recombinant inbred strains between BALB/c and C57BL/6 indicated that the pattern of idiotype expression did not correlate with IgCH allotype. The C X B recombinants expressed all three idiotype patterns that were observed in the panel of inbred strains. Testing of allotype congenic mice between BALB/c and C57BL/6 showed that CB.20 and BC.8 mice were Id20 -, whereas BAB-14 mice were Id20 +, indicating that both VH and background (V kappa or regulatory) loci must be derived from BALB/c to obtain Id20 expression. The difference in the frequency of idiotype expression observed between BALB/c and BAB-14 mice indicates that the IgCH locus may exert a quantitative influence on the expression of this light chain. To examine the Id20 -, Id5 + antibodies of C57BL/6 mice, anti- GAC hybridomas were prepared. Of 16 C57BL/6-derived anti- GAC monoclonal antibodies, six were reactive with anti- Id5 and not with anti- Id20 . Isoelectric focusing of the purified kappa light chains from three of these antibodies revealed two distinct spectrotypes that co-migrated with the two known VK1GAC spectrotypes observed with A/J anti- GAC light chains. Idiotypic analysis of in vitro recombinants between the heavy and light chains of A/J and C57BL/6 monoclonal antibodies demonstrated that the C57BL/6 light chains were idiotypically similar to A/J light chains when they were free in solution or paired with A/J heavy chains. These results demonstrate that C57BL/6 mice can express a light chain that is very similar, if not identical, to the VK1GAC light chain, although the light chain is expressed in lower frequency and is paired with a distinct VH structure, which can mask expression of one of the VK1GAC idiotypes. These effects on V kappa expression map to at least three genetic loci: VH, CH, and an unlinked locus.

摘要

VK1GAC轻链代表A/J小鼠对A组链球菌碳水化合物(GAC)抗体反应中所采用的主要Vκ结构。使用两种对VK1GAC轻链具有特异性的抗独特型抗血清,即抗Id5和抗Id20,来检测一系列在重链恒定区(IgCH)同种异型位点存在差异的近交系小鼠品系中的抗GAC抗体反应。除了IgCHb(C57BL/6J)和IgCHf(CE/J)之外,大多数IgCH同种异型小鼠的正常血清和免疫血清中均表达这两种独特型。C57BL/6J小鼠表达Id5,但不表达Id20,而CE/J小鼠两种独特型均不表达。对BALB/c和C57BL/6之间的重组近交系进行检测表明,独特型表达模式与IgCH同种异型不相关。C×B重组体表达了在近交系小鼠组中观察到的所有三种独特型模式。对BALB/c和C57BL/6之间的同种异型同源近交系小鼠进行检测表明,CB.20和BC.8小鼠为Id20阴性,而BAB-14小鼠为Id20阳性,这表明VH和背景(Vκ或调节)位点都必须来自BALB/c才能获得Id20表达。在BALB/c和BAB-14小鼠之间观察到的独特型表达频率差异表明,IgCH位点可能对这种轻链的表达产生定量影响。为了检测C57BL/6小鼠的Id20阴性、Id5阳性抗体,制备了抗GAC杂交瘤。在16种源自C57BL/6的抗GAC单克隆抗体中,有6种与抗Id5反应,但不与抗Id20反应。对其中三种抗体纯化的κ轻链进行等电聚焦分析,发现了两种不同的光谱型,它们与用A/J抗GAC轻链观察到的两种已知VK1GAC光谱型共迁移。对A/J和C57BL/6单克隆抗体的重链和轻链之间的体外重组体进行独特型分析表明,当C57BL/6轻链在溶液中游离或与A/J重链配对时,其独特型与A/J轻链相似。这些结果表明,C57BL/6小鼠可以表达一种与VK1GAC轻链非常相似(如果不是完全相同)的轻链,尽管这种轻链表达频率较低,并且与一种独特的VH结构配对,这可能会掩盖VK1GAC独特型之一的表达。这些对Vκ表达的影响至少映射到三个基因位点:VH、CH和一个不连锁的位点。

相似文献

1
Influence of the immunoglobulin heavy chain locus on expression of the VK1GAC light chain.免疫球蛋白重链基因座对VK1GAC轻链表达的影响。
J Immunol. 1984 Jul;133(1):465-70.
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The mouse heavy chain variable region marker, J606-GAC, is not restricted to particular B cell isotypes or subsets.小鼠重链可变区标志物J606-GAC并不局限于特定的B细胞同种型或亚群。
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Complete heavy and light chain variable region sequence of anti-arsonate monoclonal antibodies from BALB/c and A/J mice sharing the 36-60 idiotype are highly homologous.来自BALB/c和A/J小鼠、具有36-60独特型的抗砷酸盐单克隆抗体的完整重链和轻链可变区序列高度同源。
J Immunol. 1984 Nov;133(5):2603-9.

引用本文的文献

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