Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.

Sequence analyses of three immunoglobulin G anti-virus antibodies reveal their utilization of autoantibody-related immunoglobulin Vh genes, but not V lambda genes.
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三种免疫球蛋白 G 抗病毒抗体的序列分析揭示了它们利用自身抗体相关的免疫球蛋白 Vh 基因,而不是 V lambda 基因。

DOI:
10.1172/jci116105
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发表时间:
1992
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Chen,PP
Chen,PP
中科院分区:
--
文献类型:
--
作者:
Huang,DF;Olee,T;Masuho,Y;Matsumoto,Y;Carson,DA;Chen,PP

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抗体库的累积序列分析显示,大多数自身抗体和发育调节抗体共享一小组生殖系Ig可变区(V)基因。这些发现促使人们推测某些自身抗体具有发育的重要性,并且可能有助于维持成人抗体库的稳态。为了批判性地评价这一假设,首先需要确定抗外源物质的人抗体中V基因的使用。不幸的是,只有少数这样的抗体具有其重链和轻链的特征。为了纠正这种情况,我们采用锚定聚合酶链反应快速克隆和分析三种抗病毒IgG抗体的表达V基因。结果表明,这三个重链V(Vh)基因与已知的自身抗体相关的Vh基因高度同源。相反,V λ 1亚组的两个轻链V(VL)基因与非自身抗体相关的种系V λ 1基因相似。与针对病毒和细菌的几种抗体的报道的Vh和VL序列一起,数据显示,许多抗病原体抗体可以使用编码自身抗体的相同的一小组Vh基因,但是不同的VL基因不同于自身抗体相关的VL基因。因此,只有一小部分潜在功能性种系Vh基因被反复使用以产生正常抗体库中的大多数抗体,而不管它们与自身或非自身的反应性如何。
Accumulated sequence analyses of the antibody repertoire have revealed that most autoantibodies and developmentally regulated antibodies share a small set of germline Ig-variable region (V) genes. The findings have prompted speculation that certain autoantibodies are of developmental importance and may be instrumental in maintaining homeostasis of the adult antibody repertoire. In order to evaluate this hypothesis critically, it is first necessary to determine the V gene usage in human antibodies against foreign substances. Unfortunately, only a few such antibodies have had their heavy and light chains characterized. To rectify the situation, we adapted the anchored polymerase chain reaction to clone and analyze rapidly the expressed V genes for three anti-virus IgG antibodies. The results show that all three heavy chain V (Vh) genes are highly homologous to the known autoantibody-related Vh genes. In contrast, two light chain V (VL) genes of the V lambda 1 subgroup are similar to a non-autoantibody-related germline V lambda 1 gene. Taken together with the reported Vh and VL sequences of several antibodies against viruses and bacteria, the data show that many antipathogen antibodies may use the same small set of Vh genes that encode autoantibodies, but diverse VL genes that are distinct from autoantibody-related VL genes. Thus, only a small portion of the potentially functional germline Vh genes are used recurrently to generate most antibodies in a normal antibody repertoire, regardless of their reactivities with either self or non-self.
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影响因子: --
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