In vivo cell penetration and intracellular transport of anti-Sm and anti-La autoantibodies.
Anti-nuclear autoantibodies (ANA) are the hallmark of systemic autoimmune diseases. Yet, the in vivo function of ANA remains controversial to a large extent due to the intracellular nature of their antigenic targets. It has been reported that a subset of autoantibodies can penetrate live cells and translocate into the subcellular compartments containing the corresponding antigens. The studies presented herein show that murine anti-Sm and anti-La monoclonal autoantibodies can also enter a variety of cell types from different animal species and that the cell penetration activity is not isotype-restricted. Interestingly, only mAb with cross-reactivity against double-stranded DNA did enter cells. Both these autoantibodies rapidly accumulate in the nucleus of viable cells but display different penetration kinetics. In co-localization experiments, monoclonal autoantibodies did not accumulate significantly within endocytic vesicles containing dextran, suggesting that they are internalized by mechanisms distinct from conventional receptor-mediated endocytosis. This report represents the first evidence that anti-La and anti-Sm autoantibodies are capable of entering live cells. Our observations support the notion that the phenomenon of intracellular autoantibodies may have a larger scope than previously reported and are consistent with a potential pathogenic role for ANA.
Deng
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SX
Department of Immunology and Microbiology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 695, Rochester, NY 14642, USA.
Hanson
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Sanz
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D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001323:Autoantibodies / Q000378:metabolism*; D001324:Autoantigens / Q000276:immunology*; D001693:Biological Transport, Active / Q000276:immunology; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000276:immunology; D002467:Cell Nucleus / Q000276:immunology / Q000378:metabolism; D004705:Endocytosis / Q000276:immunology*; D006801:Humans; D007424:Intracellular Fluid / Q000276:immunology* / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D019463:Mice, Inbred MRL lpr; D008969:Molecular Sequence Data; D051381:Rats; D012261:Ribonucleoproteins / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear; D013552:Swine; D014407:Tumor Cells, Cultured; D055517:snRNP Core Proteins; D000097585:SS-B Antigen
D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D001324:Autoantigens; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen