Exp Mol Med.  2011 Jun;43(6):350-357. 10.3858/emm.2011.43.6.038.

Regulation of B cell activating factor (BAFF) receptor expression by NF-kappaB signaling in rheumatoid arthritis B cells

• Woo YJ
• Yoon BY
• Jhun JY
• Oh HJ
• Min S
• Cho ML
• Park SH
• Kim HY
• Min JK

• KMID: 1107376
• DOI: http://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-kappaB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-kappaB p65, NF-kappaB 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-kappaB inhibitors. NF-kappaB p65, NF-kappaB 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-kappaB inhibitors in PBMCs and B cells from normal controls. We also showed reduction in expression of BAFF-R via inhibition of the NF-kappaB 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-kappaB blocking therapy is another choice for controlling B cells in autoimmune diseases such as RA.

Keyword

B-cell activation factor receptor; B-cell activating factor; B-lymphocytes; NF-kappaB; rheumatoid arthritis

MeSH Terms

Arthritis, Rheumatoid/genetics/*metabolism/pathology/physiopathology
B-Cell Activating Factor/genetics/metabolism
B-Cell Activation Factor Receptor/genetics/*metabolism
B-Lymphocytes/*drug effects/immunology/metabolism/pathology
Cell Separation
Cells, Cultured
Disease Progression
Enzyme Inhibitors/pharmacology
Flow Cytometry
Gene Expression Regulation/immunology
Humans
Immunohistochemistry
NF-kappa B/*metabolism
Signal Transduction/immunology
Synovial Membrane/*pathology
T-Lymphocytes/drug effects/immunology/metabolism/pathology
Transcriptional Activation/drug effects