REGULATION OF MOUSE CD72 GENE-EXPRESSION DURING B-LYMPHOCYTE DEVELOPMENT

CD72 is a 45-kDa transmembrane glycoprotein that is predominantly expr essed on cells of the B lineage except plasma cells. previously, we id entified the 255-bp minimal mouse CD72 promoter capable of tissue-spec ific and developmental stage-specific expression. DNase I footprinting analysis of the 255-bp CD72 promoter revealed three protected element s, footprint (FP) I, FP II, and FP III, FP II, which extends from nucl eotide -189 to -169 of the mouse CD72 promoter, exhibited both tissue- specific and developmental stage-specific activity that was reflective of the activity of the CD72 gene in vivo, In this report, we show tha t FP Ii is specifically recognized by the transcription factor B cell- specific activator protein (BSAP). Mutations eliminating the binding o f BSAP in reporter constructs also eliminated the increase of reporter activity in B cells. In addition, cotransfections with reporter const ructs plus different amount of expression plasmids for BSAP showed tha t CD72 promoter activity was up-regulated by BSAP in plasmacytoma cell s and T cells in a dose-dependent manner. Moreover, the expression lev el of CD72 decreased 10-fold on normal plasma cells, Compared with the presence of BSAP binding in mature B cells, the binding of BSAP was u ndetectable in those plasma cells, This study strongly suggests that B SAP-FP II interaction plays a critical role in determining the cell-ty pe specificity of the CD72 promoter, The absence of positive factors s uch as BSAP accounts for at least part of the loss of mouse CD72 expre ssion in plasma cells and thus might be common for the down-regulation of many molecules at the plasma cell stage.