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Immunoglobulin class switch recombination

W Harriman1, H Völk, N Defranoux

  • 1Department of Microbiology and Immunology, University of California, San Francisco 94143-0670.

Annual Review of Immunology
|January 1, 1993
PubMed
Summary
This summary is machine-generated.

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B lymphocytes switch immunoglobulin heavy chain production via DNA deletion. The looping out and deletion model best explains this genetic event, maintaining antibody specificity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • B lymphocytes produce immunoglobulin heavy (H) chains, initially mu.
  • These cells can switch to producing other H chain classes (gamma, epsilon, alpha) while retaining the variable (V) region, thus maintaining antigenic specificity.

Purpose of the Study:

  • To elucidate the genetic mechanism behind immunoglobulin heavy chain class switching.
  • To evaluate proposed models for the DNA deletion accompanying the switch.

Main Methods:

  • Analysis of DNA deletion products associated with immunoglobulin heavy chain class switching.
  • Comparison of experimental findings with predictions from three proposed models: homologous recombination, unequal sister chromatid exchange, and looping out and deletion.

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Main Results:

  • Products predicted by homologous recombination and unequal sister chromatid exchange models were not found.
  • By-products consistent with the looping out and deletion model, including inversions and circular DNA, were isolated.
  • Transcription of the target constant (C) region may be a prerequisite for switching.

Conclusions:

  • The looping out and deletion model is the most fitting explanation for the DNA rearrangement during immunoglobulin heavy chain class switching.
  • Switch rearrangement is mediated by a switch recombinase, with ongoing efforts to isolate its components.
  • Alternative mechanisms involving RNA processing or trans-splicing are discussed as possibilities for switching without DNA rearrangement.