High Rate of Somatic Point Mutation in vitro in and near the Variable-Region Segment of an Immunoglobulin Heavy Chain Gene

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 83; no. 18; pp. 6950 - 6953
• Main Authors: Meyer, Jutta, Jäck, Hans-Martin, Ellis, Nina, Wabl, Matthias
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-09-1986; National Acad Sciences
• Subjects: Alleles; B lymphocytes; Base Composition; Base Sequence; Biological and medical sciences; Cell Line; Cell lines; Cloning, Molecular; Codon; Codons; DNA - analysis; Feeder cells; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genetic mutation; Genetics of the immune response; Immunobiology; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Immunoglobulins; Mutation; Point mutation; Sequencing; Stop codon; Somatic mutation; Vertebrata; Immunoglobulins; Mammalia; Antibody; heavy-Peptide chain; Diversity; Inheritance
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.83.18.6950

The ``silent'' allele at the immunoglobulin heavy-chain locus in the pre-B-lymphocyte line 18-81 contains a correctly assembled gene. However, an amber termination codon within the variable-region gene segment prematurely terminates translation into complete heavy chain. Revertants that do produce heavy chain are generated at a high rate, which is termed hypermutation. By DNA sequencing of subclones, we have confirmed that whenever μ chain is produced by the usually silent allele, a true reversion is found in the DNA. Mutations are not confined to the position of the amber termination codon but are also found at other sites in and near the variable-region gene segment.