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.
Highlights
B cell activating factor (BAFF), a member of the tumor necrosis factor family and known as BLys, TALL-1, zTNF4, or THANK, is a critical cytokine in peripheral B cell survival during primary development and homeostasis (Rahman et al, 2003; Matsushita et al, 2007)
To examine B cell activation factor (BAFF) and BAFF receptor (BAFF-R) expression in synovium, samples of severe rheumatoid arthritis (RA), mild RA and OA synovium were immunostained with specific antibodies for these proteins
We demonstrated that inhibition of Nuclear factor (NF)-κB promotes decreased expression of BAFF-R in human peripheral blood mononuclear cells (PBMC) and peripheral B cells
Summary
B cell activating factor (BAFF), a member of the tumor necrosis factor family and known as BLys, TALL-1, zTNF4, or THANK, is a critical cytokine in peripheral B cell survival during primary development and homeostasis (Rahman et al, 2003; Matsushita et al, 2007). BAFF binds to three receptors, BAFF-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation Ag (BCMA) (Rahman et al, 2003; Rahman and Manser, 2004; Zhang et al, 2005; Matsushita et al, 2007; Kim et al, 2009). A/WySnJ mice, containing a mutation in BAFF-R, exhibit a phenotype that is similar to BAFF-deficient mice (Mayne et al, 2008)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
