Sainis K, Datta S K
Department of Medicine, Tupper Research Institute, Boston, MA 02111.
J Immunol. 1988 Apr 1;140(7):2215-24.
The (NZB x SWR)F1 hybrid mice (SNF1) uniformly develop lethal glomerulonephritis in marked contrast to their parents and produce nephritogenic autoantibodies that consist of highly cationic, IgG anti-DNA antibodies that share distinct cross-reactive idiotypes called IdLNF1 (idiotypes-lupus nephritis-SNF1). Herein we found that spleen cells of SNF1 mice at the late prenephritic stage, contained CD4+/CD8- and CD4-/CD8- Th that not only induced their B cells in vitro to produce highly cationic IgG autoantibodies to DNA but IdLNF1-positive IgG antibodies as well. The double-negative Th were unexpected in the SNF1 mice because they lack the lpr (lymphoproliferation) gene. We also derived IL-2-dependent CD4+/CD8- as well as CD4-/CD8- T cell lines from nephritic SNF1 mice, that could simultaneously induce IdLNF1-positive and cationic anti-DNA antibodies of IgG class. The CD4+ T cell lines consisted of "autoreactive" T cells, but not all of the lines were equal in autoantibody-inducing capability. Remarkably, the T cell lines that preferentially responded to F1-hybrid-MHC determinants, had a significantly greater ability to augment the production of pathogenic autoantibodies. The SNF1-Th could also augment autoantibody production by the NZB or SWR parent's B cells; however, IdLNF1-positive and cationic anti-DNA autoantibodies of IgG class were not induced, suggesting that the SNF1 mice possess a select population of inducible (susceptible) B cells that are committed to produce nephritogenic autoantibodies and the parental strains are deficient in such B cells. Thus, production of nephritogenic autoantibodies with IdLNF1 markers in the SNF1 mice could result from an interaction between a select population of B cells and CD4+ Th that preferentially recognize unique F1-hybrid-MHC determinants, as well as double-negative auxiliary Th.
（NZB×SWR）F1杂交小鼠（SNF1）均会发展为致死性肾小球肾炎，这与其亲本形成鲜明对比，并且会产生致肾炎性自身抗体，这些自身抗体由高度阳离子化的IgG抗DNA抗体组成，它们具有独特的交叉反应性独特型，称为IdLNF1（独特型-狼疮性肾炎-SNF1）。在此我们发现，处于肾炎前期晚期的SNF1小鼠的脾细胞含有CD4 + / CD8-和CD4- / CD8-Th，它们不仅在体外诱导其B细胞产生高度阳离子化的IgG抗DNA自身抗体，还能诱导产生IdLNF1阳性IgG抗体。双阴性Th在SNF1小鼠中出乎意料，因为它们缺乏lpr（淋巴细胞增殖）基因。我们还从患肾炎的SNF1小鼠中获得了依赖IL-2的CD4 + / CD8-以及CD4- / CD8-T细胞系，它们可以同时诱导IdLNF1阳性和IgG类阳离子抗DNA抗体。CD4 + T细胞系由“自身反应性”T细胞组成，但并非所有细胞系在诱导自身抗体的能力上都相同。值得注意的是，优先对F1杂交MHC决定簇作出反应的T细胞系，在增强致病性自身抗体产生方面具有明显更强的能力。SNF1-Th也可以增强NZB或SWR亲本B细胞的自身抗体产生；然而，未诱导出IgG类IdLNF1阳性和阳离子抗DNA自身抗体，这表明SNF1小鼠拥有一群可诱导的（易感的）B细胞，它们致力于产生致肾炎性自身抗体，而亲本菌株缺乏此类B细胞。因此，SNF1小鼠中带有IdLNF1标记的致肾炎性自身抗体的产生可能是由于一群特定的B细胞与优先识别独特的F1杂交MHC决定簇的CD4 + Th以及双阴性辅助性Th之间相互作用的结果。
