title: T-independent activation of B cells by vesicular stomatitis virus: no evidence for the need of a second signal.
abstract: Vesicular stomatitis virus (VSV) induces a T helper cell-independent IgM antibody response, whereas the IgG response is strictly T helper cell dependent. Since VSV induces B cells in complete absence of T helper cells, the question arises as to whether this induction occurs in the absence of a second signal or whether it depends upon an alternative or replacing signal 2. We therefore asked whether VSV has polyclonal B cell stimulator activity and/or whether B cell induction by VSV needs costimulation via complement or tumor necrosis factor (TNF) receptor or by natural killer (NK) cell activity. In vitro B cell proliferation assays and analysis of the in vivo antibody response in CD40-deficient mice excluded that VSV has properties of a polyclonal B cell stimulator. C3 depletion by cobra venom factor and application of anti-complement receptor antibodies showed that the T-independent IgM response was largely C3-independent except under very limiting antigen doses. Immunization of TNF receptor-deficient mice showed a normal anti-VSV IgM response, and in a cytotoxicity assay on YAC target cells there was no evidence of NK cell activation by VSV. Thus, VSV seems to induce B cells without polyclonal activation and/or C3, TNF, or NK cells functioning as a replacing second signal.
authors.affiliation: Institute of Experimental Immunology, University of Zurich, Switzerland.
authors.forename: T
authors.initials: T
authors.lastname: Fehr
authors.forename: M F
authors.initials: MF
authors.lastname: Bachmann
authors.forename: H
authors.initials: H
authors.lastname: Bluethmann
authors.forename: H
authors.initials: H
authors.lastname: Kikutani
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology; D003176:Complement C3 / Q000037:antagonists & inhibitors / Q000276:immunology; D004546:Elapid Venoms / Q000494:pharmacology; D007114:Immunization; D007075:Immunoglobulin M / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017924:Nucleopolyhedroviruses / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology*; D014759:Viral Envelope Proteins / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D019013:CD40 Antigens; D003176:Complement C3; D004546:Elapid Venoms; C028391:G protein, vesicular stomatitis virus; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C016310:cobra venom factor