International Immunology, Vol. 11, No. 10, 1709-1713,
October 1999
© 1999 Japanese Society for Immunology
The Ig heavy chain intronic enhancer core region is necessary and sufficient to promote efficient class switch recombination
1 Howard Hughes Medical Institute, The Children's Hospital, and
2 The Center for Blood Research and Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Correspondence to: F. W. Alt, Howard Hughes Medical Institute, The Children's Hospital, 300 Longwood Avenue, Boston, MA 02115, USA
The intronic IgH enhancer Eµ, which consists of the core enhancer (cEµ) flanked by 5' and 3' matrix attachment regions (MAR), has been implicated in the control of IgH locus recombination and transcription. Both cEµ and the MAR are required to enhance transcription of an IgH transgene. To elucidate the regulatory functions of cEµ versus its associated MAR in IgH class switch recombination (CSR), we have assayed ES cell lines which have targeted deletions of these elements, both individually and in combination, by the Rag-2-deficient blastocyst complementation method. Mutant B cells from chimeric mice were activated in culture and the influence of the mutations on CSR was assessed by analysis of B cell hybridomas. We find that the cEµ is necessary and sufficient for providing the functions of Eµ required for efficient CSR at the IgH locus. However, the 5' and 3' MAR sequences, as well as the known Iµ transcription start sites and the bulk of Iµ coding sequences, were dispensable for the process.
Keywords: Eµ enhancer, gene targeting, Ig class switching, matrix attachment region
3 Present address: Immunology Unit, Department of Medicine, University of Rochester Medical Center, Rochester, NY 14642, USA
Transmitting editor: D. Kitamura
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