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

Michel Cogné, Rusty Lansford, Andrea Bottaro, Jue Zhang, James Gorman, Faith Young, Hwel Ling Cheng, Frederick W. Alt

Research output: Contribution to journalArticlepeer-review

224 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)737-747
Number of pages11
JournalCell
Volume77
Issue number5
DOIs
StatePublished - Jun 3 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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