B-lymphocyte-induced maturation protein1 up-regulates the expression of B-cell maturation antigen in mouse plasma cells

Abstract

B-lymphocyte-induced maturation protein1(Blimp-1) and B-cell maturation antigen (BCMA) are essential factors in the development and survival of plasma cells. However, whether Blimp-1 could regulate the expression of BCMA is unknown. We found that the BCMA promoter region did not have typical "TATA" and "CAAT" box, but contained several potential binding sites of transcription factors, including the consensus sequences for Blimp-1, located in the "-31 to -21" and "-46 to -36" from the potential transcription initiation site of the mouse BCMA gene, respectively. Furthermore, induction of Blimp-1 over-expression significantly up-regulated the expression of BCMA and increased the BCMA promoter activity in mouse J558L plasma cells. In parallel, knockdown of Blimp-1 expression by the Blimp-1-specific shRNA significantly reduced the BCMA mRNA transcription and protein expression in J558L cells in vitro. Substitution mutation of the "-38 to -42" sequence, but not the "-23 to -27", in the BCMA promoter abolished the regulatory effect of Blimp-1 on the expression of BCMA. Importantly, Blimp-1 bound to the "GAAAC", but not its mutant "GATTC", contained BCMA promoter, as determined by competitive electrophoretic mobility shift assay (EMSA). Therefore, our data clearly suggest that Blimp-s a positive regulator of the expression of BCMA gene in mouse plasma cells.