A site in the complement receptor 2 (CR2/CD21) silencer is necessary for lineage specific transcriptional regulation

Expression of human complement receptor type 2 (CR2/CD21) is primarily rest ricted to mature a cells and follicular dendritic cells. We previously desc ribed an intronic transcriptional silencer that controls the appropriate B cell-specific and developmentally restricted expression of human CR2/CD21 i n both stably transfected cell lines and transgenic mice. Here we report th e identification of a nucleotide sequence within the 2.5 kb CR2 silencer (C RS) that is crucial to its silencer function. This site comprises a binding site for the transcriptional repressor CBF1 (RBP-J or RBP-J kappa) as well as Spl and other as yet uncharacterized proteins. A 2-bp mutation which el iminates the binding of CBF1 and other protein(s) in vitro results in loss of silencer activity in vivo. These results demonstrate the importance of t his site in regulating CR2 expression and suggest that CBF1, a component of the developmentally important Notch signaling pathway, may play a role in the control of human CR2 gene expression.