Background/Purpose: Clinical efficacy of B-cell depletion therapy underscores a pathogenic role of B cells in autoimmune diseases such as rheumatoid arthritis (RA). In addition to generating pathogenic antibodies, B cells can function as potent effector cells by an Ab-independent mechanism. RANKL is a member of the tumor necrosis factor (TNF) family and plays a key role in osteoclastogenesis and inflammatory bone loss. A recent study suggested that B cells, but not T cells, are a major source of RANKL in the joints of patients with RA. In this study, we have elucidated underlying mechanisms of RANKL expression in B cells from normal subjects and RA patients, and determined the impacts on osteoclast differentiation.

Methods: Levels of RANKL mRNA and protein in B cells from peripheral blood of normal subjects and RA patients were evaluated using quantitative RT-PCR and flow cytometry, respectively. Highly pure B cell subsets were enriched using cell sorter. To validate the functional significance of osteoclast differentiation, B cells were co-cultured with osteoclast precursor cells and the formation of tartrate-resistant acid phosphatase (TRAP)-positive cells were assessed thereafter.

 Results: In the absence of stimuli, human B cells only marginally expressed RANKL mRNA and protein. Combined stimulation of B cells with anti-Ig and anti-CD40, however, significantly induced RANKL expression. The experiments using signaling inhibitors suggested the involvement of several pathways in its expression. Among B cell subsets, switched-memory (CD27+IgD-) B cells, a normal counterpart of pathogenic B cells in the joints, expressed RANKL at the highest levels. Consistent with these findings, these subsets induced osteoclast formation as assessed by TRAP staining. Finally, switched-memory B cells from RA patients expressed RANKL at higher levels than normal subjects.

Conclusion: Our current findings shed the light on a pathogenic role of switched-memory B cells in bone damage associated with RA via production of RANKL, and regulation of RANKL expression in B cells may pave an avenue in developing a novel treatment for this devastating disease.

---

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/accentuated-expression-of-rankl-in-switched-memory-b-cells-from-patients-with-rheumatoid-arthritis/