Datta S K, Gavalchin J
Ann N Y Acad Sci. 1986;475:47-58. doi: 10.1111/j.1749-6632.1986.tb20855.x.
The investigations with the NZB X SWR model show that the development of systemic autoimmune disease is a multistep, multigene process. Severe lupus nephritis in the NZB X SWR hybrids results from the interaction of genes inherited from both the autoimmune NZB and the normal SWR parents. A similar genetic interaction occurs in the NZB X NZW hybrids, but in this model, both the parental strains are abnormal and the nature of the gene products or their mechanism of action is unknown. In the NZB X SWR model, we have been able to identify a restricted subpopulation of nephritogenic anti-DNA antibody idiotypes that are encoded by genes of the normal SWR parents. Thus, these are one set of genes that determine the development of severe lupus nephritis in the F1 hybrids. In addition, another set of genes allows for the expansion of B cells that produce such pathogenic anti-DNA idiotypes in the F1 hybrids since such B-cell clones remain dormant in the normal SWR parents. The latter category of genes, presumably specifying defects in immunoregulation, are probably inherited from the NZB parents or may be the result of complementation of genes inherited from both parents. Further investigations with the NZB X SWR model will help us define the immunoregulatory defects in SLE that are specific for the T and B cells involved in pathogenic autoantibody production.
对NZB×SWR模型的研究表明，系统性自身免疫疾病的发展是一个多步骤、多基因的过程。NZB×SWR杂交种中的严重狼疮性肾炎是由自身免疫性NZB和正常SWR亲本遗传的基因相互作用导致的。类似的基因相互作用也发生在NZB×NZW杂交种中，但在这个模型中，两个亲本菌株都是异常的，基因产物的性质或其作用机制尚不清楚。在NZB×SWR模型中，我们已经能够鉴定出由正常SWR亲本的基因编码的致肾炎抗DNA抗体独特型的一个受限亚群。因此，这些是决定F1杂交种中严重狼疮性肾炎发展的一组基因。此外，另一组基因允许在F1杂交种中产生这种致病性抗DNA独特型的B细胞扩增，因为这种B细胞克隆在正常SWR亲本中保持休眠状态。后一类基因，大概是指定免疫调节缺陷的基因，可能是从NZB亲本遗传而来的，也可能是双亲遗传基因互补的结果。对NZB×SWR模型的进一步研究将有助于我们确定系统性红斑狼疮中针对致病性自身抗体产生所涉及的T细胞和B细胞的免疫调节缺陷。
