International Immunology, Vol. 12, No. 4, 415-423,
April 2000
© 2000 Japanese Society for Immunology
In vivo cell penetration and intracellular transport of anti-Sm and anti-La autoantibodies
Department of Immunology and Microbiology, and Department of Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Box 695, Rochester, NY 14642, USA
Correspondence to: I. Sanz
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.
Keywords: autoantibody, autoimmune disease, intracellular antibodies, ribonucleoproteins, systemic lupus erythematosus
Transmitting editor: C. Martinez-A
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