Isotype switching of an immunoglobulin heavy chain transgene occurs by DNA recombination between different chromosomes

Cell. 1990 Nov 2;63(3):537-48. doi: 10.1016/0092-8674(90)90450-s.

Abstract

Transgenic mice carrying an immunoglobulin mu heavy chain transgene exhibit isotype switching of the transgene. We have now characterized the mechanism of transgene switching in these mice. The site of mu transgene insertion in one transgenic line has been localized to chromosome 5 using a series of polymorphic endogenous retroviruses as genetic markers in backcross mice. The endogenous immunoglobulin heavy chain locus resides on mouse chromosome 12, which shows that transgene isotype switching can occur between two different chromosomes even though normal antibody gene switching has generally been thought to occur within one chromosome. We find that transgene isotype switching involves interchromosomal DNA recombination, and our data suggest that the same enzymatic mechanisms mediate both normal isotype switch recombination and interchromosomal transgene switching. Our findings also support the notion that the isotype switching mechanism can induce chromosomal translocations such as observed for the c-myc gene in some B cell tumors.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Chromosome Mapping*
  • Cloning, Molecular
  • Crosses, Genetic
  • DNA / genetics
  • Genes, Immunoglobulin*
  • Immunoglobulin Heavy Chains / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Oligonucleotide Probes
  • Recombination, Genetic*
  • Restriction Mapping
  • Sequence Homology, Nucleic Acid
  • Translocation, Genetic

Substances

  • Immunoglobulin Heavy Chains
  • Oligonucleotide Probes
  • DNA

Associated data

  • GENBANK/M38389
  • GENBANK/M57241