Age-associated B cells in early drug-naive rheumatoid arthritis patients

Abstract

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterised by joint inflammation. Studies in mice and patients suffering from autoimmune diseases described a novel subset of B cells named age-associated B cells (ABCs). Moreover, a subset of synovial fluid B cells with a similar phenotype and FcRL4 expression contributes to RA pathogenesis. Newly diagnosed patients were recruited from the Newcastle Early Arthritis Clinic. B cell subsets in blood were phenotyped using flow cytometry. NanoString Immunlogy Panel was used to asses gene expression from sorted ABCs, naïve, memory and CD5+ B cells from RA patients, age-matched healthy controls and disease controls. Our work showed that there are no significant differences in the frequency of ABCs between RA patients, and disease and healthy controls. Our results also show that ABCs resemble the memory B cell phenotype regarding class-switch immunoglobulins expression. Interestingly, the FcRL4+, the Ki67+ and the T-bet expressing B cells were enriched in the ABC population. ABCs expressed high levels of HLA-DR and co-stimulatory molecules, as well as the activation marker, CD69. Gene expression analysis showed a specific gene signature for the ABCs when compared to the other B cells. KEGG analysis results showed that differentially expressed genes were enriched in the antigen presentation and the cytokine-cytokine receptor interaction pathways. Moreover, 13 genes were overexpressed in ABCs from the RA patients compared to the other control groups. This data supports the idea that ABCs have a pathogenic role in RA, potentially via T cell stimulation and migration to sites of inflammation. However, further characterisation of this subset and functional studies are needed.