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

已证实，正常小鼠经核结合蛋白(Nuc)或抗CD3抗体处理后，血清中核小体(NS)的出现与胸腺细胞的凋亡同时出现(I.P.)可以被重复地观察到。然而，在同时给予Nuc和抗CD3抗体的小鼠中，NS从循环中的清除受到抑制。这种延迟被发现是由于Nuc与NS的结合，这表明Nuc诱导的自身免疫是导致自身抗原在循环中保留时间更长的原因。在这种情况下，不仅观察到组蛋白H1和35-40 kDa蛋白酪氨酸磷酸化的增加，而且在双向凝胶电泳法中还观察到20-30 kDa蛋白的新出现，其pl为5.5-5.7。由于这些都是与Nuc相关的新发现，我正在扩大这项研究的范围，以从自身免疫的角度阐明这些分子。从连续给予Nuc的BALB/c小鼠中，成功地建立了两个针对Nuc的T细胞系：T4和T8为CD4阳性，仅限于MHC(I-Ad)。这些线条将有助于进一步分析系统性自身免疫机制。综上所述，我认为Nuc在自身免疫诱导中的作用如下。1)由于代谢衰竭，循环中的Nuc升高。2)由于胸腺中的细胞凋亡，Nuc将核小体释放到循环中。3)核小体结合的Nuc可诱导辅助性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.