The genetic basis of antibody production: a single heavy chain variable region gene encodes all molecules bearing the dominant anti-arsonate idiotype in the strain A mouse.
A nucleic acid probe specific for heavy chains bearing the cross-reactive idiotype (Id) associated with the anti-p-azophenylarsonate response of strain A mice has been prepared. Analysis of arsonate-binding Id+ hybridoma cell lines has revealed that all of them contain the same germ-line VH gene rearranged to the JH2 segment. An Id+ hybridoma which is unable to bind arsonate utilized the same VH gene, but it has apparently rearranged to the JH4 segment. Id- cell lines contain other rearranged VH genes. Analysis of DNa of strain A mice revealed that there is apparently only one germ line gene that can give rise to Id+ heavy chains. Since the Id is expressed as a large collection (greater than 50) of related but nonidentical heavy chain sequences, we conclude that their diversity is the result of a somatic mutation process. Analysis of a single hybridoma cell line (45-59) reveals that somatic mutation can operate on an Id-encoding gene and result in an antigen-binding molecule that has lost all of its Id determinants. Further analysis of the genome of strain A mice has revealed the presence of germ-line genes differing from the Id-encoding gene by at least 8 base pairs. These genes, however, apparently do not contribute to the anti-arsonate Id response.
D000818:Animals; D000916:Antibody Diversity; D000917:Antibody Formation; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics*; D004274:DNA, Recombinant; D005796:Genes; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D008805:Mice, Inbred A / Q000196:embryology / Q000276:immunology*; D009693:Nucleic Acid Hybridization; D010132:p-Azobenzenearsonate / Q000276:immunology
D004274:DNA, Recombinant; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D010132:p-Azobenzenearsonate