Bachmann M, Chang S, Bernd A, Mayet W, Meyer zum Büschenfelde K H, Müller W E
Johannes Gutenberg University of Mainz, Inst. Physiol. Chem., F.R.G.
Autoimmunity. 1991;9(2):99-107. doi: 10.3109/08916939109006745.
La (SS-B) protein is known as one major antigenic target for autoantibodies from patients with certain autoimmune diseases such as Sjogren's syndrome or Lupus Erythematosus. La protein belongs to the so called "extractable nuclear antigens". Here we report that La antigen is not restricted to the nucleus as one might deduce from the exclusive nuclear staining pattern of patient anti-La antibodies but after stimulation of serum-starved cells with 10% fetal calf serum (FCS) appears and stays for at least 45 min at the outer surface of CV-1 cells being available for binding of anti-La antibodies. In addition we found that a minor part of La antigen associates with the extracellular fibronectin network. After addition of 10% FCS to serum starved cells this extracellular autoantigen disassembled from the extracellular matrix and was taken up again by the cells. Incubation of serum starved cells with mercuric chloride, a known potent inducer of autoantibodies, also resulted in a detachment of the extracellular matrix associated La protein. From our studies it becomes likely that La protein itself is the antigen during autoimmunization. Moreover, once developed, anti-La antibodies might be able to bind to cell surface expressed La protein resulting in a damage of these cells leading to the inflammational events known to occur during disease.
La(SS - B)蛋白是某些自身免疫性疾病(如干燥综合征或红斑狼疮)患者自身抗体的主要抗原靶点之一。La蛋白属于所谓的“可提取核抗原”。在此我们报告,La抗原并不局限于细胞核,尽管从患者抗La抗体独特的核染色模式可能会推断它仅存在于细胞核中,但在用10%胎牛血清(FCS)刺激血清饥饿细胞后,它会出现在CV - 1细胞的外表面,并至少停留45分钟,可与抗La抗体结合。此外,我们发现一小部分La抗原与细胞外纤连蛋白网络相关联。向血清饥饿细胞中添加10% FCS后,这种细胞外自身抗原从细胞外基质中解离,并再次被细胞摄取。用已知的强效自身抗体诱导剂氯化汞孵育血清饥饿细胞,也会导致与细胞外基质相关的La蛋白脱离。从我们的研究来看,La蛋白本身很可能是自身免疫过程中的抗原。此外,一旦产生,抗La抗体可能能够结合细胞表面表达的La蛋白,导致这些细胞受损,进而引发疾病过程中已知的炎症事件。