Regulation of mouse CD72 gene expression during B lymphocyte development

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.

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.