James J A, Harley J B
College of Medicine, University of Oklahoma Health Sciences Center and U.S. Department of Veteran's Affairs Medical Center, Oklahoma City 73104, USA.
J Immunol. 1998 Jan 1;160(1):502-8.
Anti-Sm is a common and specific autoantibody found in systemic lupus erythematosus. The peptide PPPGMRPP from Sm B/B' is an early target of the autoimmune response in some anti-Sm-positive human patients. After immunization with this peptide on a MAP backbone, rabbits develop anti-Sm autoantibodies with B cell epitope spreading of the autoimmune response as well as other features of lupus autoimmunity. Various strains of inbred mice have been immunized with peptide PPPGMRPP or PSQQVMTP (nonantigenic region of Sm B/B') in Freund's adjuvant or with no peptide. All peptide-immunized mouse strains eventually develop high titers of specific anti-peptide of immunization Abs. Mice immunized with Freund's adjuvant alone have no measurable Ab binding to the PPPGMRPP peptide. With time, nearly half the mouse strains tested develop Abs that react with additional regions of Sm B/B' and Sm D. All the regions bound by mouse serum are major epitopes of the human systemic lupus erythematosus anti-Sm response. These same strains also develop significant anti-Sm and anti-nuclear ribonucleoprotein titers. In addition, some of these strains demonstrate positive anti-nuclear Abs and anti-dsDNA Abs. Experiments with congenic H-2 mice demonstrate that the H-2 region does not play a role in spreading the immune response from the peptide of immunization to other epitopes of the spliceosome. These results present a new murine model of B cell epitope spreading and lupus autoimmunity induced by peptide immunization that is strain specific and not apparently dependent upon the loci at H-2.
抗Sm抗体是系统性红斑狼疮中常见且特异性的自身抗体。来自Sm B/B'的肽段PPPGMRPP是一些抗Sm阳性人类患者自身免疫反应的早期靶点。用该肽段在MAP骨架上免疫兔子后，兔子会产生抗Sm自身抗体，出现自身免疫反应的B细胞表位扩展以及狼疮自身免疫的其他特征。用肽段PPPGMRPP或PSQQVMTP（Sm B/B'的非抗原区域）在弗氏佐剂中免疫或不使用肽段免疫多种近交系小鼠。所有经肽段免疫的小鼠品系最终都会产生高滴度的针对免疫肽段的特异性抗体。仅用弗氏佐剂免疫的小鼠没有可检测到的与PPPGMRPP肽段结合的抗体。随着时间推移，近一半测试的小鼠品系会产生与Sm B/B'和Sm D其他区域反应的抗体。小鼠血清结合的所有区域都是人类系统性红斑狼疮抗Sm反应的主要表位。这些相同的品系还会产生显著的抗Sm和抗核核糖核蛋白滴度。此外，其中一些品系表现出阳性抗核抗体和抗双链DNA抗体。用同源H-2小鼠进行的实验表明，H-2区域在将免疫反应从免疫肽段扩展到剪接体的其他表位方面不起作用。这些结果呈现了一种由肽段免疫诱导的B细胞表位扩展和狼疮自身免疫的新小鼠模型，该模型具有品系特异性，且显然不依赖于H-2位点。
