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The murine IgG1/IgE class switch program.

G Siebenkotten1, C Esser, M Wabl

  • 1Institut für Genetik, Universität zu Köln, FRG.

European Journal of Immunology
|July 1, 1992
PubMed
Summary
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Interleukin-4 (IL-4) directs immunoglobulin class switching. Studies show that switching to IgE may frequently occur sequentially through an intermediate IgG1 switch in IgE-producing cells.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Cytokines, such as interleukin-4 (IL-4), are key regulators of immunoglobulin (antibody) class switching.
  • IL-4 is known to direct class switching towards both IgG1 and IgE antibody isotypes.

Purpose of the Study:

  • To investigate the molecular mechanisms and potential sequential nature of immunoglobulin class switching to IgE.
  • To analyze the active and inactive alleles of the immunoglobulin heavy chain (IgH) locus in IgE-producing cells.

Main Methods:

  • Restriction endonuclease analysis of the IgH locus in IgE-producing cells.
  • In vitro stimulation of cells with lipopolysaccharide and IL-4.
  • In vivo stimulation of cells with antigen.

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Main Results:

  • In vitro, silent alleles preferentially switched to IgG1 (gamma 1) when stimulated with IL-4.
  • In vivo, both active and inactive alleles switched to IgE (epsilon) when stimulated by antigen.
  • Approximately 30% of recombined switch regions (S mu/S epsilon) contained switch gamma 1 (S gamma 1) sequences, indicating prior switching to IgG1.

Conclusions:

  • The presence of S gamma 1 sequences suggests that switching to IgE may often occur sequentially, proceeding through an intermediate IgG1 switch.
  • Between 30% and 100% of IgE switching might occur via a sequential pathway involving IgG1.