title: Virus or a hapten-carrier complex can activate autoreactive B cells by providing linked T help.
abstract: We investigated the mechanism leading to an IgG autoantibody response in two transgenic mouse lines expressing the glycoprotein of vesicular stomatitis virus (VSV-G). Previous experiments have shown that these animals do not mount a transgene-specific IgG response upon stimulation with purified VSV-G or infection with recombinant vaccinia virus expressing VSV-G. However, infection of VSV-G transgenic animals with wild-type vesicular stomatitis virus, serotype Indiana, readily induced VSV-G-specific, neutralizing IgG autoantibodies. We have tested whether this labile state of tolerance reflected differential availability of VSV-G-specific T help. For this, we immunized transgenic mice with the self-antigen VSV-G covalently coupled to sperm-whale myoglobulin (VSV-G-SWM), to provide new T helper epitopes that are linked to the B cell epitope; co-injected uncoupled VSV-G and SWM served as control. High titers of VSV-G specific IgG autoantibodies were detected in serum of mice immunized with VSV-G-SWM but not after co-injection of uncoupled VSV-G and SWM. Transgenic animals depleted of CD4+ T cells prior to injection of VSV-G-SWM failed to mount an IgG response. Priming of transgenic mice with the foreign carrier did not accelerate the IgG autoantibody response to VSV-G-SWM, suggesting that B cells were limiting the rate of the response. Thus, self-reactive B cells could be triggered to produce IgG, if they received linked T help specific for a foreign carrier determinant provided either by a classical carrier determinant or a virus.
authors.affiliation: Department of Pathology, Institute for Experimental Immunology, Zürich, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Steinhoff
authors.forename: C
authors.initials: C
authors.lastname: Burkhart
authors.forename: H
authors.initials: H
authors.lastname: Arnheiter
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R
authors.initials: R
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006241:Haptens; D007108:Immune Tolerance; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D009211:Myoglobin / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: C028391:G protein, vesicular stomatitis virus; D006241:Haptens; D008562:Membrane Glycoproteins; D009211:Myoglobin; D014759:Viral Envelope Proteins