The role of somatic mutation in the generation of the protective humoral immune response against vesicular stomatitis virus

Immunity. 1996 Dec;5(6):639-52. doi: 10.1016/s1074-7613(00)80277-0.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / genetics*
  • Antibody Affinity
  • Antibody Formation
  • Base Sequence
  • Cells, Cultured
  • Chlorocebus aethiops
  • Cricetinae
  • Hybridomas
  • Immunoglobulin G / genetics*
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin kappa-Chains / genetics
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neutralization Tests
  • Point Mutation*
  • Rhabdoviridae Infections / immunology*
  • Sequence Homology, Amino Acid
  • Vero Cells
  • Vesicular stomatitis Indiana virus / immunology*

Substances

  • Antibodies, Viral
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Variable Region
  • Immunoglobulin kappa-Chains

Associated data

  • GENBANK/Z75748
  • GENBANK/Z75749
  • GENBANK/Z75750
  • GENBANK/Z75751
  • GENBANK/Z75752
  • GENBANK/Z75753
  • GENBANK/Z75754
  • GENBANK/Z75755
  • GENBANK/Z75756
  • GENBANK/Z75757
  • GENBANK/Z75758
  • GENBANK/Z75759
  • GENBANK/Z75760
  • GENBANK/Z75761
  • GENBANK/Z75762
  • GENBANK/Z75763
  • GENBANK/Z75764
  • GENBANK/Z75765
  • GENBANK/Z75766
  • GENBANK/Z75767
  • GENBANK/Z75768
  • GENBANK/Z75769
  • GENBANK/Z75770
  • GENBANK/Z75771
  • GENBANK/Z75772
  • GENBANK/Z75773
  • GENBANK/Z75774
  • GENBANK/Z75775