Regulation of human epsilon germline transcription: role of B-cell-specific activator protein.

Abstract

Germline transcripts initiate from promoters upstream of the immunoglobulin switch region, and are necessary to target the appropriate switch region for recombination and switching. Different cytokines activate transcription at the appropriate germline promoter. Because binding sites for B-cell-specific activator protein (BSAP) are located upstream of several switch regions in the immunoglobulin heavy chain gene cluster, BSAP might play a role in the regulation of germline transcription and isotype switching. We investigated whether BSAP plays a role in the transcriptional regulation of the epsilon germline promoter in human B cells. Our results showed that BSAP plays a role in both IL-4-dependent induction and CD40-mediated upregulation of human epsilon germline transcription. BSAP is unique among the transcription factors that regulate epsilon germline expression, because it is B cell specific, and is at the merging point of two signalling pathways that are critical for IgE switching.