The NZB X SWR model of lupus nephritis. I. Cross-reactive idiotypes of monoclonal anti-DNA antibodies in relation to antigenic specificity, charge, and allotype. Identification of interconnected idiotype families inherited from the normal SWR and the autoimmune NZB parents.
The NZB X SWR model of lupus nephritis. I. Cross-reactive idiotypes of monoclonal anti-DNA antibodies in relation to antigenic specificity, charge, and allotype. Identification of interconnected idiotype families inherited from the normal SWR and the autoimmune NZB parents.
复制标题
狼疮性肾炎的NZB X SWR模型。
作者：
J. Gavalchin;R. Seder;S. K. Datta
狼疮性肾炎的发病率在自身免疫性NZB小鼠中很低，但当它们与正常的SWR小鼠杂交时，几乎100%的雌性F1杂交小鼠（SNF1）发展为致死性肾小球肾炎。在以前的研究中，我们发现SNF1小鼠产生的抗DNA自身抗体在同种型、电荷和抗原特异性模式方面与NZB父母产生的抗体有质的不同。在这里，我们研究了独特型交叉反应之间的65个单克隆抗DNA抗体，来自4个NZB和7个SNF1小鼠。从65株抗DNA单克隆抗体中选出15株免疫家兔，制备了15株抗独特型抗体库。我们在大量的自身抗体中确定了10个交叉反应性独特型（CRI）家族。其中5个CRI家族仅限于SNF1来源的阳离子抗DNA抗体，强烈交叉反应的成员主要是IgG2b自身抗体与正常SWR亲本的同种异型。阳离子抗DNA CRI家族可以被分组为称为Id564簇的相互关联的簇。其他五个抗DNA CRI家族不限于任何特定的亲本同种异型或电荷，尽管其中两个CRI仅由SNF1衍生的自身抗体共享，并且其中四个CRI家族也可以被分组为称为Id512簇的独特相关簇。在10个CRI家族中的7个家族中，检测到的独特型决定簇接近抗DNA抗体的抗原结合位点。结果表明，由SNF1小鼠产生的抗DNA自身抗体的独特型库与NZB亲本不同，并且由来自正常SWR亲本的基因编码的由SNF1小鼠产生的潜在致病性（阳离子）抗体可以被鉴定为不同的CRI家族。在随附的论文中，我们证明了这些抗DNA CRI家族在狼疮肾炎发展中的作用。
The incidence of lupus nephritis is low in autoimmune NZB mice, but when they are crossed with normal SWR mice, almost 100% of the female F1 hybrids (SNF1) develop lethal glomerulonephritis. In a previous study we showed that anti-DNA auto-antibodies produced by the SNF1 mice were qualitatively different from those made by the NZB parents with respect to their isotype, charge, and antigenic specificity patterns. Here we studied idiotypic cross-reactions among the 65 monoclonal anti-DNA antibodies that were derived from four NZB and seven SNF1 mice. A library of 15 anti-idiotypic antibodies were prepared by immunizing rabbits with 15 monoclonal anti-DNA antibodies selected from the panel of 65. We identified 10 cross-reactive idiotype (CRI) families among this large collection of autoantibodies. Five of these CRI families were restricted to cationic anti-DNA antibodies that were exclusively of SNF1 origin, and the strongly cross-reacting members were predominantly IgG2b auto-antibodies with the allotype of the normal SWR parent. The cationic anti-DNA CRI families could be grouped into an interrelated cluster called the Id564 cluster. The other five anti-DNA CRI families were not restricted to any particular parental allotype or charge, although two of these CRI were shared exclusively by SNF1-derived autoantibodies and four of these CRI families could also be grouped into an idiotypically interrelated cluster called the Id512 cluster. In the case of seven out of the 10 CRI families, the idiotypic determinants detected were close to the antigen-binding site of the anti-DNA antibodies. The results indicate that the idiotypic repertoire of anti-DNA autoantibodies produced by the SNF1 mice is different from the NZB parents, and potentially pathogenic (cationic) antibodies produced by the SNF1 mice that are encoded by genes from the normal SWR parent can be identified as distinct CRI families. In the accompanying paper we demonstrate the role of these anti-DNA CRI families in the development of lupus nephritis.