Details

Autor(en) / Beteiligte

• Ota, Yuri
• Niiro, Hiroaki
• Ota, Shun-Ichiro
• Ueki, Naoko
• Tsuzuki, Hirofumi
• Nakayama, Tsuyoshi
• Mishima, Koji
• Higashioka, Kazuhiko
• Jabbarzadeh-Tabrizi, Siamak
• Mitoma, Hiroki
• Akahoshi, Mitsuteru
• Arinobu, Yojiro
• Kukita, Akiko
• Yamada, Hisakata
• Tsukamoto, Hiroshi
• Akashi, Koichi

Titel

Generation mechanism of RANKL(+) effector memory B cells: relevance to the pathogenesis of rheumatoid arthritis

Ist Teil von

• Arthritis research & therapy, 2016-03, Vol.18 (68), p.67-67, Article 67

Ort / Verlag

England: BioMed Central Ltd

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• The efficacy of B cell-depleting therapies for rheumatoid arthritis underscores antibody-independent functions of effector B cells such as cognate T-B interactions and production of pro-inflammatory cytokines. Receptor activator of nuclear factor κB ligand (RANKL) is a key cytokine involved in bone destruction and is highly expressed in synovial fluid B cells in patients with rheumatoid arthritis. In this study we sought to clarify the generation mechanism of RANKL(+) effector B cells and their impacts on osteoclast differentiation. Peripheral blood and synovial fluid B cells from healthy controls and patients with rheumatoid arthritis were isolated using cell sorter. mRNA expression of RANKL, osteoprotegerin, tumor necrosis factor (TNF)-α, and Blimp-1 was analyzed by quantitative real-time polymerase chain reaction. Levels of RANKL, CD80, CD86, and CXCR3 were analyzed using flow cytometry. Functional analysis of osteoclastogenesis was carried out in the co-culture system using macrophage RAW264 reporter cells. RANKL expression was accentuated in CD80(+)CD86(+) B cells, a highly activated B-cell subset more abundantly observed in patients with rheumatoid arthritis. Upon activation via B-cell receptor and CD40, switched-memory B cells predominantly expressed RANKL, which was further augmented by interferon-γ (IFN-γ) but suppressed by interleukin-21. Strikingly, IFN-γ also enhanced TNF-α expression, while it strongly suppressed osteoprotegerin expression in B cells. IFN-γ increased the generation of CXCR3(+)RANKL(+) effector B cells, mimicking the synovial B cell phenotype in patients with rheumatoid arthritis. Finally, RANKL(+) effector B cells in concert with TNF-α facilitated osteoclast differentiation in vitro. Our current findings have shed light on the generation mechanism of pathogenic RANKL(+) effector B cells that would be an ideal therapeutic target for rheumatoid arthritis in the future.