title: Vesicular stomatitis virus glycoprotein displaying retrovirus-like particles induce a type I IFN receptor-dependent switch to neutralizing IgG antibodies.
abstract: Vesicular stomatitis virus (VSV) infection rapidly induces IFN-alphabeta that confers initial survival, whereas long-term protection is mediated by neutralizing IgG responses. Because coadministration of IFN-alphabeta can enhance Ab responses against soluble Ags, we addressed whether virus-induced IFN-alphabeta also had an impact on the induction of neutralizing Ab responses. To this end, we generated apathogenic retrovirus-like particles (VLP) displaying the VSV gp (VLP-VSV). Reminiscent of live VSV, VLP-VSV induced VSV-neutralizing IgM responses that switched to IgG in a T help-dependent manner. In type I IFN receptor-deficient (IFNAR(-/-)) mice, VLP-VSV injection elicited neutralizing IgM, whereas the IgG switch was absent. The lack of subclass switch was associated with a reduced germinal center reaction. Conditional knockout mice with a lymphocyte-specific IFNAR ablation showed normal Ab responses against VLP-VSV, as well as against live VSV. Thus, IFNAR triggering critically promoted the T help-dependent subclass switch of virus-neutralizing Ab responses against VLP-VSV. Interestingly, in the context of VLP-VSV as well as VSV immunization, IFNAR triggering of B lymphocytes did not play a critical role.
authors: Division of Immunology, Paul-Ehrlich-Institut, Langen, Germany.
authors: Patricia
authors: P
authors: Bach
authors: Elisabeth
authors: E
authors: Kamphuis
authors: Bernhard
authors: B
authors: Odermatt
authors: Gerd
authors: G
authors: Sutter
authors: Christian J
authors: CJ
authors: Buchholz
authors: Ulrich
authors: U
authors: Kalinke
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000235:genetics / Q000276:immunology*; D012190:Retroviridae / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; C028391:G protein, vesicular stomatitis virus; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; D053633:Receptor, Interferon alpha-beta