title: The role of somatic mutation in the generation of the protective humoral immune response against vesicular stomatitis virus.
abstract: During most clinically relevant infections with cytopathic viruses, neutralizing antibodies are generated early, i.e., within the first week of infection. As early as 4 days after immunization of mice with vesicular stomatitis virus (VSV), a cytopathic virus closely related to rabies virus, hybridomas could be isolated that secreted virus-neutralizing IgGs. Such antibodies were devoid of somatic mutations, showed high binding avidities (approximately 10(9) M-1), and used V gene fragments predominantly belonging to the VHQ52 and VK19-28 families. In contrast, most secondary and hyperimmune response IgGs isolated 12 and 150 days after infection used several additional V gene combinations. These, which used the VHQ52/VK19-28 combination of early IgGs, were point mutated but showed only marginally enhanced binding avidities. Since all VHQ52/ VK19-28-positive IgGs bound to one subsite within the major antigenic site of VSV-G irrespective of the presence or absence of somatic point mutations, fine specificity diversification of secondary and hyperimmune responses was achieved by newly appearing V gene combinations.
authors.affiliation: Institute of Experimental Immunology, Zürich, Switzerland.
authors.forename: U
authors.initials: U
authors.lastname: Kalinke
authors.forename: E M
authors.initials: EM
authors.lastname: Bucher
authors.forename: B
authors.initials: B
authors.lastname: Ernst
authors.forename: A
authors.initials: A
authors.lastname: Oxenius
authors.forename: H P
authors.initials: HP
authors.lastname: Roost
authors.forename: S
authors.initials: S
authors.lastname: Geley
authors.forename: R
authors.initials: R
authors.lastname: Kofler
authors.forename: R M
authors.initials: RM
authors.lastname: Zinkernagel
authors.forename: H
authors.initials: H
authors.lastname: Hengartner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000235:genetics*; D000915:Antibody Affinity; D000917:Antibody Formation; D001483:Base Sequence; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D006825:Hybridomas; D007074:Immunoglobulin G / Q000235:genetics*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017354:Point Mutation; D018353:Rhabdoviridae Infections / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D007145:Immunoglobulin kappa-Chains