Recombination between antibody heavy chain variable-region genes: evidence for gene conversion.
The murine hybridoma line B1-8.delta 1 secretes monoclonal IgD lambda 1 antibodies specific for the hapten (4-hydroxy-3-nitrophenyl)acetyl (NP). The variable (V) region of these antibodies is defined by a characteristic pattern of idiotopes. A spontaneous V-region variant (B1-8.V1) with altered idiotope pattern was selected. The structural variation is confined to the V region of the heavy chain. It was shown previously that the variant V region is encoded by a gene that was generated by a crossover between the rearranged VDJ gene of the wild type (B1-8.delta 1) and a neighboring germ-line VH gene. In the present study the nucleotide sequence of coding and flanking regions of the VH gene expressed in variant B1-8.V1 was determined. Wild-type and variant VH genes differ at 15 positions in a region between leader sequence and codon 66. The sequence of the region carrying the substitutions is identical to the sequence of the corresponding region in a neighboring germ-line VH gene. This implies that the variant VH gene was generated by a mechanism of recombination more complicated than single crossover. Gene conversion as the mechanism of the recombination is discussed.
D000818:Animals; D010582:Bacteriophage lambda / Q000235:genetics; D001483:Base Sequence; D001666:Binding Sites, Antibody / Q000235:genetics*; D003001:Cloning, Molecular; D004262:DNA Restriction Enzymes; D004274:DNA, Recombinant / Q000032:analysis*; D005785:Gene Conversion; D005796:Genes; D005838:Genotype; D006825:Hybridomas / Q000276:immunology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007130:Immunoglobulin Idiotypes / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D009693:Nucleic Acid Hybridization
D004274:DNA, Recombinant; D007143:Immunoglobulin Heavy Chains; D007130:Immunoglobulin Idiotypes; D007135:Immunoglobulin Variable Region; D004262:DNA Restriction Enzymes