International Immunology, Vol. 13, No. 8, 1003-1012,
August 2001
© 2001 Japanese Society for Immunology
Deletional analyses reveal an essential role for the hs3b/hs4 IgH 3' enhancer pair in an Ig-secreting but not an earlier-stage B cell line
Hunter College and Graduate Center of The City University of New York, 695 Park Avenue, New York, NY 10021, USA
Correspondence to: L. A. Eckhardt
The Ig heavy chain (IgH) locus is controlled by multiple regulatory sequences mapping both within the IgH transcription unit (Eµ) and downstream (3') of IgH coding sequences (hs3a, hs1,2, hs3b and hs4). Enhancer knockout studies in mice have implicated Eµ in the control of IgH variable region gene assembly, but single-enhancer knockouts involving the 3' IgH enhancers have yet to shed light on their function. Transfection studies in mice and cell lines have suggested that the 3' enhancers behave similarly to a locus control region as first identified in the ß-globin locus. We have exploited this property to form mini-loci in a surface Ig+ and an Ig-secreting cell line as a means for studying the functions of the 3' IgH enhancers. Importantly, this experimental system allows for the analysis of enhancer function within the context of chromatin. The mini-loci consisted of an Ig
2b transcription unit linked to the four murine 3' IgH enhancers. Using targeted deletions of enhancer pairs within these mini-loci, we have discovered a critical and apparently developmentally regulated role for the hs3b/hs4 enhancer pair in IgH transgene expression.
Keywords: antibodies, B lymphocytes, gene regulation, molecular biology
1 Present address: Department of Pathology, Joan and Sanford I. Weill Medical College, Cornell University, 1300 York Avenue, New York, NY 10021, USA
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