Research Project
Grant-in-Aid for Scientific Research (C)
Objective. To investigate the role of BAFF, APRIL and their receptors in the pathogenesis of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).Results. By exon-specific PCR/SSCP, we identified a novel polymorphism, P21R, in BR3 gene. P21R is located in the cystein-rich domain of BR3, a specific receptor for BAFF, and could be functionally important. To investigate the reverse-signal through membrane BAFF, we constructed cDNA for membrane BAFF, which was not cleaved by furin convertase, by site-directed mutagenesis. Expression of membrane BAFF was observed on transfected Jurkat cells by flow cytometry. When we analyzed the expression of BR3, TACI and BCMA on each peripheral B cell subset by flow cytometry, BR3 was highly expressed on naive B cells while BCMA was highly expressed on plasmablasts. The number of plasmablasts was increased in patients with SLE. Synovial fibroblast-like cells synthesized APRIL when they were cultured in the presence of TNF-a and IFN-y. BCMA-Ig, which was common receptor for BAFF and APRIL, but not BR3-Ig, receptor for BAFF, inhibited the proliferation of synovial fibroblast-like cells in the presence of TNF-α and IFN-γ.Conclusions. These data suggest that BCMA has important role in the survival of plasmablasts in SLE patients. APRIL is associated with the proliferation of synovial fibroblast-like cells in autocrine fashon. APRIL and BAFF could be a therapeutic target in the treatment of autoimmune disease.
All 2008 2007 2006 Other
All Journal Article (9 results) (of which Peer Reviewed: 3 results) Presentation (5 results)
Arthritis Rheum 58
Pages: 1248-57
Rheumatology 47
Pages: 158-64
Rheumatology (in press)
Ann Rheum Dis 66
Pages: 320-4
Pages: 320-324
Ann Rheum Dis 65
Pages: 508-14
Int J Mol Med 17
Pages: 875-9
