Regulation of B cell activating factor (BAFF) receptor expression by NF-κB signaling in rheumatoid arthritis B cells
Open Access
- 1 January 2011
- journal article
- Published by Springer Science and Business Media LLC in Experimental & Molecular Medicine
- Vol. 43 (6), 350-7
- https://doi.org/10.3858/emm.2011.43.6.038
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.Keywords
This publication has 33 references indexed in Scilit:
- TGF-β-treated antigen presenting cells suppress collagen-induced arthritis through the promotion of Th2 responsesExperimental & Molecular Medicine, 2010
- B Cell Receptor-Mediated Sustained c-Rel Activation Facilitates Late Transitional B Cell Survival through Control of B Cell Activating Factor Receptor and NF-κB2Published by The American Association of Immunologists ,2009
- BAFF-R promotes cell proliferation and survival through interaction with IKKβ and NF-κB/c-Rel in the nucleus of normal and neoplastic B-lymphoid cellsBlood, 2009
- B cell activation factor (BAFF) is a novel adipokine that links obesity and inflammationExperimental & Molecular Medicine, 2009
- Systemic autoimmunity in BAFF‐R‐mutant A/WySnJ strain miceEuropean Journal of Immunology, 2008
- Characterisation of the cannabinoid receptor system in synovial tissue and fluid in patients with osteoarthritis and rheumatoid arthritisArthritis Research & Therapy, 2008
- NF-κB pathway inhibitors preferentially inhibit breast cancer stem-like cellsBreast Cancer Research and Treatment, 2007
- DCs induce CD40-independent immunoglobulin class switching through BLyS and APRILNature Immunology, 2002
- BAFF: A fundamental survival factor for B cellsNature Reviews Immunology, 2002
- Function and Activation of NF-kappaB in the Immune SystemAnnual Review of Immunology, 1994