Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.

Structural characteristics of the variable regions of immunoglobulin genes encoding a pathogenic autoantibody in murine lupus.
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编码鼠狼疮致病性自身抗体的免疫球蛋白基因可变区的结构特征。

DOI:
10.1172/jci114469
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发表时间:
1990
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
Hahn,BH
Hahn,BH
中科院分区:
--
文献类型:
--
作者:
Tsao,BP;Ebling,FM;Roman,C;Panosian-Sahakian,N;Calame,K;Hahn,BH

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我们研究了几种单克隆抗双链(ds) DNA抗体加速年轻的NZB X NZW F1雌性小鼠狼疮肾炎和诱导BALB/c小鼠狼疮肾炎的能力。在这两种菌株中鉴定出的两种病原体具有先前与肾源性相关的特征:IgG2a同型和IdGN2独特型的表达。两种致病抗体都使用了来自VHJ558和VK9亚家族的基因组合。两种弱致病菌均不能加速幼年BW小鼠的肾炎,但在BALB/c小鼠中诱发狼疮性肾炎。它们都表达IdGN2;一个是阳离子的IgG3,另一个是IgG2a。其他单克隆抗体(一些IgG2a,一个idgn2阳性)没有加速或诱导肾炎。我们克隆并测序了一种病原性自身抗体的免疫球蛋白基因的可变区。没有独特的V、D或J基因片段,也没有证据表明产生多样性的异常机制被用于构建该抗体。这些数据反对系统性红斑狼疮个体使用独特的异常Ig基因来构建致病性自身抗体亚群。相反,主要的异常可能是免疫调节。图片
We have studied several monoclonal anti-double-stranded (ds) DNA antibodies for their ability to accelerate lupus nephritis in young NZB X NZW F1 female mice and to induce it in BALB/c mice. Two identified as pathogens in both strains have characteristics previously associated with nephritogenicity: expression of IgG2a isotype and IdGN2 idiotype. Both pathogenic antibodies used the combination of genes from the VHJ558 and VK9 subfamilies. Two weak pathogens failed to accelerate nephritis in young BW mice, but induced lupus nephritis in BALB/c mice. They both express IdGN2; one is cationic and an IgG3, the other is an IgG2a. Additional MAbs (some IgG2a, one IdGN2-positive) did not accelerate or induce nephritis. We have cloned and sequenced the variable regions of the immunoglobulin genes of one pathogenic autoantibody. No unique V, D, or J gene segments and no evidence of unusual mechanisms in generating diversity were used to construct this antibody. These data argue against use of unique abnormal Ig genes by systemic lupus erythematosus individuals to construct pathogenic autoantibody subsets. Instead, the major abnormality may be immunoregulatory.Images
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