BAFF‐R gene induced by IFN‐γ in multiple myeloma cells is related to NF‐κB signals

Abstract

B-cell activating factor (BAFF) is a potent cell-survival factor expressed in many haematopoietic cells. BAFF regulates B-cell survival, differentiation and proliferation by binding to three tumour necrosis factor receptors: transmembrane activator, calcium modulator and cyclophilin ligand interactor; B-cell maturation antigen; and BAFF receptor (BAFF-R). Although BAFF-R is produced by interferon gamma (IFN-γ), the underlying mechanism remains elusive. In this study, we examined the effects of IFN-γ on BAFF-R expression in cultured human multiple myeloma cells (KM3) both at the transcriptional and posttranscriptional levels. Incubation of KM3 cells with IFN-γ elevated the expression of BAFF-R mRNA and protein levels. IFN-γ elicited marked enhancement of the human BAFF-R promoter activity and nuclear factor kappa B (NF-κB) DNA binding activity. NF-κB dependent on the human BAFF-R gene might be regulated via a transcriptional event through one putative NF-κB site on the BAFF-R gene promoter. These results provide a molecular mechanism for the increase in expression of the BAFF-R gene that is induced by proinflammatory cytokines in responsive cells.