Extensive somatic mutation in the Ig heavy chain V genes in a late primary anti-hapten immune response.
Somatic mutations and cell lineage relationships were examined in a large panel of hybridomas derived from a single mouse 21 days after a primary immunization with NP-CGG. Among 21 lambda-bearing anti-NP hybridomas 18 distinct cell lineages were observed. Ten of the hybridomas used the V186-2 gene which is the most frequently utilized VH gene in the anti-NP response. Analysis of DNA sequence of the entire VH region of these antibodies revealed extensive somatic mutations. The selection for certain codon changes and the level of mutation observed is comparable to that observed in an early secondary anti-NP response. An unexpected observation was that one-third of the hybridomas produced IgM antibodies. Two IgM antibodies expressing the V186-2 gene contained extensive mutations in the VH region. These results indicate that once the somatic mutation process is initiated, it progresses rapidly and continues for at least two weeks during the development of the response. A highly mutated repertoire of memory B cells is formed by three weeks post-immunization that can be rapidly utilized to generate the secondary immune response.
Tao
W
W
Department of Biology, Yale University School of Medicine, New Haven, CT 06510.
Hardardottir
F
F
Bothwell
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AL
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D004277:DNA, Single-Stranded / Q000096:biosynthesis / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006241:Haptens / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007075:Immunoglobulin M / Q000096:biosynthesis; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D007138:Immunoglobulin delta-Chains / Q000235:genetics; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D009596:Nitrophenols / Q000276:immunology*; D010648:Phenylacetates; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D004277:DNA, Single-Stranded; D006241:Haptens; D007143:Immunoglobulin Heavy Chains; D007144:Immunoglobulin J-Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D007138:Immunoglobulin delta-Chains; D007145:Immunoglobulin kappa-Chains; D009596:Nitrophenols; D010648:Phenylacetates; D012333:RNA, Messenger; C026242:4-hydroxy-5-nitrophenyl acetic acid