Shores E W, Eisenberg R A, Cohen P L
J Immunol. 1986 May 15;136(10):3662-7.
MRL/Mp-+/+ (+/+) and MRL/Mp-lpr/lpr (lpr) mice spontaneously produce the SLE-specific anti-nuclear antibody, anti-Sm. Previous work on the clonality and specificity of the anti-Sm response has suggested that the Sm antigen itself induces this autoantibody. In the present work, we have directly investigated the immunogenicity of Sm. In short-term cultures, Sm antigen was shown to be important for the de novo generation of anti-Sm PFC in vitro. The addition of purified Sm to cultures of spleen cells from anti-Sm-positive lpr mice augmented the number of anti-Sm PFC on day 4. Also, the addition of Fab anti-Sm to such cultures inhibited the generation of anti-Sm PFC, probably by blocking determinants on endogenous Sm. The ability of the autoantigen to initiate anti-Sm generation in vivo was investigated by hyperimmunizing +/+ mice with Sm from rabbit or mouse sources. Such mice specifically produced antibodies that recognized both rabbit and mouse Sm as determined by ELISA. The IgG subclass distribution of these induced antibodies was similar to that of spontaneous anti-Sm antibodies found in older mice of the same strain. Our data indicate that the Sm antigen can both initiate and augment production of the anti-Sm autoantibody. These findings provide additional evidence that the spontaneous anti-Sm response in SLE is antigen driven.
MRL/Mp-+/+（+/+）和MRL/Mp-lpr/lpr（lpr）小鼠可自发产生系统性红斑狼疮特异性抗核抗体——抗Sm抗体。先前关于抗Sm反应的克隆性和特异性的研究表明，Sm抗原本身可诱导这种自身抗体产生。在本研究中，我们直接探究了Sm的免疫原性。在短期培养中，Sm抗原被证明对体外抗Sm抗体形成细胞（PFC）的从头产生很重要。将纯化的Sm添加到抗Sm阳性lpr小鼠的脾细胞培养物中，可在第4天增加抗Sm PFC的数量。此外，向此类培养物中添加Fab抗Sm抗体可能通过阻断内源性Sm上的决定簇来抑制抗Sm PFC的产生。通过用来自兔或小鼠来源的Sm对+/+小鼠进行超免疫，研究了自身抗原在体内引发抗Sm产生的能力。通过酶联免疫吸附测定法（ELISA）确定，此类小鼠特异性产生了识别兔和小鼠Sm的抗体。这些诱导抗体的IgG亚类分布与在同一品系的老年小鼠中发现的自发抗Sm抗体相似。我们的数据表明，Sm抗原既能引发又能增强抗Sm自身抗体的产生。这些发现为系统性红斑狼疮中自发的抗Sm反应是由抗原驱动的这一观点提供了更多证据。
