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Mechanism of class switching.

B K Birshtein1, D R Katzenberg, A Weinreb

  • 1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.

Annals of the New York Academy of Sciences
|January 1, 1988
PubMed
Summary

This study provides the first molecular description of unequal sister chromatid exchange in antibody genes. It suggests that deletion of Cmu-associated tandem repeats may be a key step in class switch recombination in B cells.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genetics

Background:

  • Antibody genes undergo complex rearrangements during B cell development.
  • Class switch recombination (CSR) is a critical process for generating antibody diversity.
  • Unequal sister chromatid exchange (iSC E) is a mechanism of genetic recombination.

Purpose of the Study:

  • To provide the first molecular description of unequal sister chromatid exchange (iSC E) in antibody genes.
  • To delineate the DNA sequences mediating class switch recombination (CSR) in normal B cells.
  • To investigate the frequency of subclass switching in B cells.

Main Methods:

  • Genomic Southern analysis of five IgG2-producing hybridomas.
  • Characterization of DNA breakpoints involved in CSR.

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Main Results:

  • Documented the action of unequal sister chromatid exchange (iSC E) on antibody genes.
  • Identified sequences mediating class switch recombination (CSR) in normal B cells.
  • Observed successive subclass switching in 2 of 8 hybridomas, suggesting CSR may be frequent.
  • Found 5' breakpoints 5' to Cmu-associated tandem repeats and 3' breakpoints within C gamma-associated tandem repeats.

Conclusions:

  • Unequal sister chromatid exchange (iSC E) plays a role in antibody gene diversification.
  • Class switch recombination (CSR) in mature B cells may involve the deletion of Cmu-associated tandem repeats.
  • Cmu-associated tandem repeats might function as a separately regulated DNA element.