Translocation of the nuclear autoantigen La to cell surface: assembly and disassembly with the extracellular matrix.
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.
Bachmann
M
M
Johannes Gutenberg University of Mainz, Inst. Physiol. Chem., F.R.G.
Chang
S
S
Bernd
A
A
Mayet
W
W
Meyer zum Büschenfelde
K H
KH
Müller
W E
WE
D001324:Autoantigens / Q000276:immunology / Q000378:metabolism*; D015551:Autoimmunity; D001693:Biological Transport, Active; D002462:Cell Membrane / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes; D005109:Extracellular Matrix / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology; D008627:Mercuric Chloride / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D012261:Ribonucleoproteins; D000097585:SS-B Antigen
D001324:Autoantigens; D000939:Epitopes; D008627:Mercuric Chloride; D012261:Ribonucleoproteins; D000097585:SS-B Antigen