Somatically mutated forms of a major anti-p-azophenylarsonate antibody variable region with drastically reduced affinity for p-azophenylarsonate. By-products of an antigen-driven immune response?
The pivotal role played by antigen in the clonal selection of B cells for initial participation in an immune response is well established. Antigen selective mechanisms ensure that antigen-binding antibodies are produced during all stages of the immune response. However, antibodies that lack specificity for the immunogen might also be produced during the course of an antigen-driven immune response . It has been suggested that, through idiotype-antiidiotype network interactions within the immune system, production of antibodies that lack specificity for the immunogen but that share idiotopes with antigen-binding antibodies could result (1). In addition, data obtained by a number of investigators suggest that somatic mutation of antibody V region genes occurs at a rate of 10(-3)/basepair/cell division in B cells participating in an immune response (2, 3). One outcome of such V region structural alteration could be antibodies that lack, or have drastically reduced affinity for the immunogen . We sought to identify and characterize some of the antibody by-products of the antigen-driven immune response that are expected to be created by the mechanisms described above.
Manser
T
T
Department of Molecular Biology, Princeton University, New Jersey 08544.
Parhami-Seren
B
B
Margolies
M N
MN
Gefter
M L
ML
D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000235:genetics / Q000276:immunology*; D000915:Antibody Affinity; D000941:Antigens / Q000276:immunology; D001391:Azo Compounds / Q000276:immunology*; D001483:Base Sequence; D006433:Hemocyanins / Q000276:immunology; D006825:Hybridomas / Q000276:immunology; D007114:Immunization; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008805:Mice, Inbred A; D008969:Molecular Sequence Data; D009154:Mutation; D012333:RNA, Messenger / Q000235:genetics; D010132:p-Azobenzenearsonate / Q000276:immunology*
D000906:Antibodies; D000941:Antigens; D001391:Azo Compounds; D007135:Immunoglobulin Variable Region; D012333:RNA, Messenger; D010132:p-Azobenzenearsonate; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin