A class switch control region at the 3' end of the immunoglobulin heavy chain locus

Cell. 1994 Jun 3;77(5):737-47. doi: 10.1016/0092-8674(94)90057-4.


We replaced the IgH 3' enhancer (3'EH) region with a neomycin resistance gene in ES cells and generated chimeric mice in which all mature lymphocytes were either heterozygous (3'EH+/-) or homozygous (3'EH-/-) for the mutation. In vitro activated 3'EH-/- B cells responded similarly to 3'EH+/- B cells with respect to proliferation and secretion of IgM and IgG1 but were specifically deficient in IgG2a, IgG2b, IgG3, and IgE secretion. These isotype deficiencies correlated with a deficiency in accumulation of transcripts from and class switching to affected CH genes. In vivo, chimeric mice containing only 3'EH-/- B cells were deficient in serum IgG2a and IgG3. We propose that the 3'EH-/- mutation disrupts the activity of a regulatory region that influences heavy chain class switching to several different CH genes that lie as far as 100 kb upstream of the mutation.

Publication types

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

MeSH terms

  • Animals
  • Chimera
  • Gene Rearrangement, B-Lymphocyte, Heavy Chain
  • Genes, Immunoglobulin*
  • Genes, Switch*
  • Heterozygote
  • Homozygote
  • Humans
  • Immunoglobulin Heavy Chains / genetics*
  • Immunoglobulin Isotypes / genetics
  • Mice
  • Mice, Transgenic
  • Mutation
  • Phenotype
  • Restriction Mapping
  • Transcription, Genetic


  • Immunoglobulin Heavy Chains
  • Immunoglobulin Isotypes