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Related Experiment Videos

Efficient immune responses in mice lacking N-region diversity

S Gilfillan1, M Bachmann, S Trembleau

  • 1Institut de Génétique et de Biologie Moléculaire et Cellulaire, (INSERM/CNRD/ULP) Illkirch, C. U. de Strasbourg, France.

European Journal of Immunology
|November 1, 1995
PubMed
Summary

Mice lacking terminal deoxynucleotidyl transferase (TdT) show reduced N-region diversity, impacting T and B cell receptors. Surprisingly, their immune responses remain effective, challenging the necessity of N-region diversity for a functional adaptive immune system.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Terminal deoxynucleotidyl transferase (TdT) is crucial for V(D)J recombination.
  • TdT introduces N-region nucleotides, contributing to the diversity of T cell receptors (TCRs) and immunoglobulin (Ig) variable regions.
  • N-region diversity is widely considered essential for generating a broad and effective T and B cell repertoire.

Purpose of the Study:

  • To investigate the impact of absent N-region diversity on immune responses.
  • To determine if T and B cell repertoires lacking N-region diversity can mount effective and specific immune responses.
  • To re-evaluate the established role of N-region diversity in adaptive immunity.

Main Methods:

  • Utilized genetically engineered mice with a null mutation in the TdT gene (TdT0 mice).

Related Experiment Videos

  • Analyzed the immunoglobulin and T cell receptor repertoires of TdT0 mice, focusing on CDR3 loop length and diversity.
  • Assessed the efficiency and specificity of immune responses in TdT0 mice compared to wild-type controls.

    • Main Results:

    • TdT0 mice exhibited immunoglobulin and T cell receptor repertoires largely devoid of N-region diversity.
    • The CDR3 loops in TdT0 mice were significantly shorter and less diverse than in wild-type mice.
    • Despite reduced repertoire diversity, TdT0 mice demonstrated surprisingly normal immune response efficiency and specificity.

    Conclusions:

    • The absence of N-region diversity does not necessarily impair the development of effective T and B cell repertoires.
    • Immune responses can be efficient and specific even with limited CDR3 diversity.
    • These findings challenge the long-held assumption that N-region diversity is a prerequisite for a functional adaptive immune system.