Anti-DNA antibody enhancing factor Nucleobindin and autoimmunity-elucidation of its pathophysiology and molecular cell mechanism.

正常小鼠腹腔注射核结合蛋白（Nuc）或抗cd3抗体（i. p.），可重复性观察到血清核小体（NS）的出现和胸腺细胞凋亡。然而，同时给予Nuc和抗cd3抗体的小鼠，NS从循环中的清除被延缓。发现这种延迟是由于Nuc与NS的结合，这表明Nuc诱导自身免疫是自身抗原在循环中滞留时间较长的原因。在这种情况下，不仅组蛋白H1增加，35-40kDa蛋白酪氨酸磷酸化，而且在2D凝胶电泳中还观察到20-30kDa蛋白的新出现，其pl为5.5-5.7。因为这些都是与nuc相关的新发现，我正在扩展研究，以阐明这些分子在自身免疫方面的作用。在连续给予Nuc的BALB/c小鼠中成功建立了两种特异性的T细胞系；T4和T8系CD4阳性，局限于MHC （I-Ad）。这些细胞系将有助于进一步分析系统自身免疫机制。综上所述，我总结出Nuc在自身免疫诱导中的作用如下。1)代谢衰竭导致循环中Nuc升高。Nuc与核小体结合，诱导辅助性T细胞产生抗dna抗体。

It has been confirmed that the appearance of serum nucleosome (NS) together with apoptosis in the thymus in normal mice given nucleobindin (Nuc) or anti-CD3 antibody intraperitoneally (i. p.) could be reproducibly observed. However, the clearance of NS from circulation was retarded in mice give both Nuc and anti-CD3 antibody. This retardation was found to be due to the binding of Nuc to NS,suggesting that induction of autoimmunity by Nuc is responsible for longer retention of autoantigens in the circulation. In such cases, not only the increment of histone H1 and tyrosine-phosphorylation of 35-40kDa proteins but also the newly appearance of 20-30kDa proteins with pl 5.5-5.7 in 2D gel electrophoresis were observed. Because these were Nuc-associated new findings, I am extending the study for the elucidation of these molecule in terms of autoimmunity. The establishment of two T cell lines that are specific for Nuc was successful from BALB/c mice given Nuc continuously ; lines T4 and T8 were positive for CD4 and restricted to MHC (I-Ad). These lines will be useful for further analysis of systemic aoutoimmunity mechanisms. Taken together, I conclude as the role of Nuc in autoimmunity induction, as follows. 1) elevation of Nuc in the circulation due to metabolic failure. 2) release of nucleosome in to the circulation due to apoptosis in the thymus by Nuc. 3) Nuc bound with nucleosome induces helper T cells for anti-DNA antibody production.