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Related Experiment Videos

Human IgG allotypes co-occurring in more than one IgG subclass

E van Loghem, G de Lange, A M van Leeuwen

    Vox Sanguinis
    |January 1, 1982
    PubMed
    Summary

    An excess of immunoglobulin allotypes was observed, not explained by gene duplication. These extra markers were found on IgG2 and IgG1 molecules, suggesting a mutation in gamma-subclass DNA.

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    Area of Science:

    • Immunogenetics
    • Molecular immunology
    • Human genetics

    Background:

    • Immunoglobulin allotypes are inherited markers on antibody proteins.
    • An excess of allotypes in a single haplotype is unusual and challenges existing genetic models.
    • Specific allotypes are associated with different immunoglobulin gamma (IgG) subclasses.

    Purpose of the Study:

    • To investigate the genetic basis of an unexplained excess of immunoglobulin allotypes.
    • To identify the specific IgG subclass carrying the supernumerary allotypes.
    • To propose a molecular mechanism for the observed allotype inheritance pattern.

    Main Methods:

    • Isolation of IgG3 molecules using gel filtration and protein A absorption.
    • Separation of IgG subclasses (IgG1, IgG2, IgG3) via immune absorption techniques.

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  • Analysis of immunoglobulin allotypes on isolated subclasses.

    • Main Results:

    • Excess allotypes were not found on IgG3 molecules, despite initial association with gamma 3 chains.
    • Supernumerary allotypes were identified on IgG2 molecules in one case.
    • The other case revealed the excess allotypes on IgG1 molecules.
    • These findings indicate the aberrant allotypes are not linked to the original IgG3 locus.

    Conclusions:

    • The observed excess of immunoglobulin allotypes is not due to gene duplication.
    • A mutation within a homologous DNA region of gamma-subclass genes is hypothesized.
    • This mutation could explain the presence of allotypes on different IgG subclasses than expected.