title: Regulation of B cell activating factor (BAFF) receptor expression by NF-ΚB signaling in rheumatoid arthritis B cells.
abstract: B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-ΚB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-ΚB p65, NF-ΚB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was analyzed by flow cytometry, realtime PCR and confocal staining after treatment with NF-ΚB inhibitors. NF-ΚB p65, NF-ΚB p50, BAFF, and BAFF-R were highly expressed in severe RA synovium relative to mild RA synovium or OA synovium. BAFF-R expression was reduced by NF-ΚB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-ΚB pathway in PBMCs of RA patients. BAFF/BAFF-R signaling is an important mechanism of pathogenesis in RA and that BAFF-R reduction by NF-ΚB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA.
authors.affiliation: The Rheumatism Research Center Catholic Research Institute of Medical Science The Catholic University of Korea Seoul 137-040, Korea.
authors.forename: Yun Ju
authors.initials: YJ
authors.lastname: Woo
authors.forename: Bo Young
authors.initials: BY
authors.lastname: Yoon
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Jhun
authors.forename: Hye Jwa
authors.initials: HJ
authors.lastname: Oh
authors.forename: Se Won
authors.initials: SW
authors.lastname: Min
authors.forename: Mi La
authors.initials: ML
authors.lastname: Cho
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Ho Youn
authors.initials: HY
authors.lastname: Kim
authors.forename: Jun Ki
authors.initials: JK
authors.lastname: Min
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism; D053265:B-Cell Activation Factor Receptor / Q000235:genetics / Q000378:metabolism*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D002478:Cells, Cultured; D018450:Disease Progression; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D016328:NF-kappa B / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D013583:Synovial Membrane / Q000473:pathology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D053264:B-Cell Activating Factor; D053265:B-Cell Activation Factor Receptor; D004791:Enzyme Inhibitors; D016328:NF-kappa B; C505719:TNFSF13B protein, human