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Related Experiment Videos

An example of idiotypic mimicry

A Grandien1, J Andersson, D Portnoi

  • 1Unite d'Immunobiologie, CNRS URA1961, Institut Pasteur, Paris, France.

European Journal of Immunology
|July 1, 1997
PubMed
Summary

Transgenic immunoglobulin expression influences natural antibody production. Transgenic mice show high levels of endogenous IgM with cross-reactive idiotypes, suggesting mimicry through B cell selection.

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Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Transgenic immunoglobulin (TGIg) systems allow studying the impact of specific antibody expression on endogenous antibody repertoires.
  • The chosen transgenic model enables normal endogenous immunoglobulin gene recombination and early TGIg secretion, with distinct serological markers for differentiation.

Purpose of the Study:

  • To evaluate the impact of transgenic immunoglobulin expression on the endogenous antibody repertoire.
  • To investigate the characteristics of endogenous antibodies produced in the presence of a specific TGIg.

Main Methods:

  • Analysis of endogenous antibody repertoires in transgenic mice using mitogen-driven limiting dilution cultures and single-cell assays.
  • Generation and analysis of hybridomas from spleen cells of unmanipulated transgenic animals.
  • Serological characterization of TGIg and endogenous immunoglobulins (Ig).

Main Results:

  • A high frequency of splenic B cells and plasma cells in transgenic animals produced IgM with B1.8-cross-reactive idiotypes.
  • Hybridoma analysis confirmed idiotype-positive IgM production was not correlated with transgene expression levels.
  • Endogenous idiotype-positive Ig exhibited variable affinities, generally lower than the transgene-encoded idiotype, with diverse V regions distinct from the transgenic B1.8.

Conclusions:

  • Transgenic immunoglobulin expression significantly shapes the endogenous antibody repertoire.
  • The findings suggest a mechanism of idiotypic mimicry driven by intercellular selection based on degenerate V region reactivities.
  • Endogenous antibody responses in transgenic settings can display cross-reactivity without direct clonal derivation from the transgene.

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