title: Virus-induced autoantibody response to a transgenic viral antigen.
abstract: The induction of autoantibodies and their possible role in the pathogenesis of autoimmune disease are poorly understood. Involvement of infectious agents has been suspected, but direct evidence is sparse. Whether immunological unresponsiveness to self by antibody-forming B cells is maintained by clonal abortion, clonal anergy or suppression, or how the scenario of interactions between helper T cells, B cells and antigen-presenting cells is distorted in autoantibody responses, is being analysed and widely debated. To evaluate tolerance of neutralizing B-cell responses we used transgenic mice expressing the cell membrane associated glycoprotein (G) of vesicular stomatitis virus (VSV) as self-antigen. We show that autoantibodies to VSV-G cannot be induced by VSV-G in adjuvant or by recombinant vaccinia virus expressing VSV-G, but are triggered by infection with wild-type VSV. The data show that helper T-cell tolerance is crucial in maintenance of B-cell non-reactivity and that cognate T-B recognition is necessary to break tolerance of self-reactive B cells. These results may help to understand mechanisms of virus-induced autoimmunity.
authors.affiliation: Institute of Pathology, University of Zurich, Switzerland.
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: S
authors.initials: S
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Chambers
authors.forename: R A
authors.initials: RA
authors.lastname: Lazzarini
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: H
authors.initials: H
authors.lastname: Arnheiter
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology; D015870:Gene Expression; D007108:Immune Tolerance / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011994:Recombinant Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D014777:Virus Diseases / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C028391:G protein, vesicular stomatitis virus; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins