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Related Experiment Videos

Multiple VH gene segments encode murine antistreptococcal antibodies.

R M Perlmutter, J L Klotz, M W Bond

    The Journal of Experimental Medicine
    |January 1, 1984
    PubMed
    Summary

    Murine antibodies against group A streptococcal carbohydrate (GAC) primarily use specific antibody gene segments. This study reveals genetic mechanisms contributing to antibody diversity and shared features in anti-GAC responses.

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    Area of Science:

    • Immunology
    • Molecular Genetics
    • Bacteriology

    Background:

    • Most mouse strains produce diverse antibody responses to group A streptococcal carbohydrate (GAC).
    • Previous studies indicated murine anti-GAC antibodies are mainly restricted to IgM and IgG3 subclasses.
    • A significant portion of A/J anti-GAC antibodies share a common light chain (VK1GAC), despite heterogeneity.

    Purpose of the Study:

    • To investigate the genetic basis of diversity in murine anti-GAC antibodies.
    • To identify specific variable heavy (VH) and variable kappa (VK) gene segments involved in the anti-GAC response.
    • To explore the evolutionary mechanisms shaping antibody gene families.

    Main Methods:

    • Protein sequencing of anti-GAC antibodies.
    • DNA sequencing of antibody variable gene segments.

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  • Spectrotypic and idiotypic analysis to define antibody clonotypes.

    • Main Results:

    • Multiple, highly homologous VH gene segments contribute to anti-GAC antibody generation.
    • A common framework sequence, related to the VK27 subgroup, likely defines the VK1GAC light chain.
    • A/J anti-GAC VH regions show high protein-level homology (95%) with BALB/c anti-inulin VH sequences, suggesting shared gene families.

    Conclusions:

    • The anti-GAC antibody response in mice is shaped by the utilization of specific, closely related VH gene segments.
    • A conserved light chain (VK1GAC) and homologous VH regions contribute to the characteristic antibody repertoire against GAC.
    • The findings suggest genetic mechanisms allowing for the evolution of multiple homologous germline VH gene segments with divergent flanking sequences.