Investigating the consequences of B-cell and fibroblasts interactions in rheumatoid arthritis

Research output: Contribution to conference (unpublished)Paperpeer-review

Abstract

Wilson IL 1,2, Vidal-Pedrola G1, McGettrick HM1, Scheel-Toellner D2, Pratt AG1, Filer, A2, Isaacs JD1, Anderson AE1

(1) Translational and Clinical Research Institute, Newcastle University, UK.

(2) Centre for Translational Inflammation Research, University of Birmingham, UK.


Introduction
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by synovial joint inflammation. Previously our group has shown that B-cells from early RA upregulate receptors that bind ligands commonly found on or secreted by RA synovial fibroblasts (SFb). We hypothesise that the upregulation of these molecules promotes migration of B-cells into the synovium and enables interactions with SFb, creating a potential new therapeutic target for the treatment of RA.

Method
B-cells from healthy volunteers were stimulated for 2-3 days with TLR7 and TLR9 ligands, anti IgG/M, anti CD40L and IL-4. SFb donated from RA or osteoarthritis (OA) patients undergoing joint replacement were cultured between passage 2-6 and stimulated with TNF-alpha and IFN-gamma before co-culture. Transmigration was determined using phase-contract microscopy after 2 hours of co-culture. Surface activation marker expression and cytokine levels were determined after 5 days of co-culture by flow cytometry and ELISA, respectively.

Results and discussion
Stimulated B-cells upregulated the adhesion receptor CD97 and chemokine receptors CXCR3 and CX3CR1, and adhered and transmigrated through SFb to a greater extent than unstimulated B-cells. Co-cultures of stimulated SFb and B-cells significantly enhanced survival of B-cells, and may potentially increase the activation marker CD69 on B cells. In addition, co cultures of stimulated B-cells co-cultured with stimulated SFb, significantly increased the production of IL-6. This suggests that there could be direct or indirect interactions between B-cells and SFb taking place resulting in prolonged B-cell survival, activation and the secretion of the pro-inflammatory cytokine, IL-6, during in vitro co-culture.
Original languageEnglish
Publication statusPublished - 2023

Fingerprint

Dive into the research topics of 'Investigating the consequences of B-cell and fibroblasts interactions in rheumatoid arthritis'. Together they form a unique fingerprint.

Cite this