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Polymorphism in immunoglobulin heavy chains suggesting gene conversion.

S H Clarke, J L Claflin, S Rudikoff

    Proceedings of the National Academy of Sciences of the United States of America
    |May 1, 1982
    PubMed
    Summary

    Heavy chain variable region sequences of phosphocholine-binding antibodies reveal multiple VH genes encode these proteins. Gene conversion likely explains the origin of antibody 6G6.

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    Area of Science:

    • Immunology
    • Molecular Biology
    • Genetics

    Background:

    • Monoclonal antibodies targeting phosphocholine (PCho) are crucial in immune responses.
    • Understanding the genetic basis of antibody diversity is essential for immunology.
    • Previous studies identified the T15 germline VH segment as a key component in PCho-binding antibodies.

    Purpose of the Study:

    • To determine the complete heavy (H) chain variable region (V region) sequences of three PCho-binding monoclonal antibodies from CBA mice.
    • To investigate the genetic origins and diversity of VH genes encoding PCho-binding antibodies.
    • To explore the potential mechanisms, such as gene conversion, contributing to VH gene evolution.

    Main Methods:

    • Sequencing of complete heavy chain variable region (amino acids 1-118) from three monoclonal antibodies.

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  • Comparison of determined VH sequences with known germline VH segments (T15, V11) and their alleles.
  • Analysis of amino acid differences to infer genetic relationships and evolutionary processes.

    • Main Results:

    • Two of the three antibodies possessed VH sequences identical to the C57BL allelic form of T15, differing from the BALB/c T15 germline at four positions.
    • The third antibody, HP101.6G6 (6G6), utilized a VH segment derived from a related VH gene, likely an allele of the BALB/c V11 gene.
    • The 6G6 VH segment exhibited seven amino acid differences from V11, with four encoded by other members of the PCho VH gene family.

    Conclusions:

    • Multiple heavy chain variable region (VH) genes are capable of encoding phosphocholine (PCho)-binding antibodies.
    • The sequence of the 6G6 VH segment is likely the result of gene conversion between at least three members of the PCho VH gene family.
    • This suggests a dynamic evolutionary process shaping the repertoire of VH genes involved in PCho recognition.