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Related Experiment Videos

Regulation of mouse CD72 gene expression during B lymphocyte development

H Ying1, J I Healy, C C Goodnow

  • 1Department of Medicine, Stanford University School of Medicine, CA 94305-5487, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|October 30, 1998
PubMed
Summary

The B cell-specific activator protein (BSAP) binds to the CD72 promoter, regulating its expression in B cells. Loss of BSAP binding in plasma cells explains decreased CD72 expression.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Gene Regulation

Background:

  • CD72 is a B lineage glycoprotein with cell-type and developmental stage-specific expression.
  • Previous studies identified a minimal mouse CD72 promoter with regulatory elements.

Purpose of the Study:

  • To investigate the role of the transcription factor BSAP in regulating CD72 gene expression.
  • To elucidate the mechanism behind CD72's cell-type specific expression, particularly its downregulation in plasma cells.

Main Methods:

  • DNase I footprinting to identify regulatory elements in the CD72 promoter.
  • Reporter construct assays to assess promoter activity in B cells and T cells.
  • Site-directed mutagenesis to disrupt BSAP binding sites.
  • Cotransfection experiments with BSAP expression plasmids.

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Main Results:

  • The footprint II (FP II) element (-189 to -169) of the CD72 promoter specifically binds the transcription factor BSAP.
  • Mutations in the FP II BSAP binding site abolished reporter activity in B cells.
  • BSAP up-regulated CD72 promoter activity in a dose-dependent manner in plasmacytoma and T cells.
  • BSAP binding was detected in mature B cells but absent in plasma cells, correlating with CD72 expression levels.

Conclusions:

  • The interaction between BSAP and the CD72 promoter's FP II element is critical for cell-type specific CD72 expression.
  • The absence of BSAP in plasma cells contributes to the downregulation of CD72 expression at this developmental stage.
  • This mechanism may be common for the regulation of other molecules during plasma cell differentiation.