Molecular characterization of virus-induced autoantibody responses.
Here we present a comprehensive molecular mapping of virus-induced autoimmune B cell responses obtained by serological identification of antigens by recombinant expression cloning analysis. Immunoscreening of cDNA expression libraries of various organs (lung, liver, and spleen) using sera from mice infected with cytopathic (vaccinia virus [VV]) or noncytopathic (lymphocytic choriomeningitis virus [LCMV]) viruses revealed a broad specificity of the elicited autoantibody response. Interestingly, the majority of the identified autoantigens have been previously described as autoantigens in humans. We found that induction of virus-induced autoantibodies of the immunoglobulin G class largely depends on the CD40-CD40L-mediated interaction between T and B cells. Furthermore, antibody titers against a number of autoantigens were comparable to the concomitantly induced antiviral antibody response. Comparison of serum reactivity against a selected panel of autoantigens after infection with VV, LCMV, or vesicular stomatitis virus showed that the different virus infections triggered distinct autoantibody responses, suggesting that virus infections may leave specific "autoantibody fingerprints" in the infected host.
Ludewig
Burkhard
B
Department of Pathology, Institute of Experimental Immunology, University Hospital Zürich, CH-8091 Zürich, Switzerland. burkhard.ludewig@kssg.ch
Krebs
Philippe
P
Metters
Helen
H
Tatzel
Jutta
J
Türeci
Ozlem
O
Sahin
Ugur
U
D000465:Algorithms; D000818:Animals; D001323:Autoantibodies / Q000737:chemistry*; D001402:B-Lymphocytes / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D019992:Databases as Topic; D015723:Gene Library; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution; D014616:Vaccinia virus / Q000378:metabolism
D001323:Autoantibodies; D019013:CD40 Antigens; D018076:DNA, Complementary; D007074:Immunoglobulin G; D023201:CD40 Ligand