Background: Immunoglobulin D (IgD) is a surface immunoglobulin that is expressed as either membrane IgD (mIgD) or secreted IgD (sIgD).Researchers have shown that sIgD is often elevated in patients with autoimmune diseases.In this study,we investigated the expression and function of immunoglobulin D receptor (IgDR) on fibroblast-like synoviocytes (FLSs) from patients with rheumatoid arthritis (RA),which are still unclear.Methods: FLSs were prepared from synovial tissues of RA patients (RA-FLSs) and healthy controls (HC-FLSs).mIgD and IgDR on FLSs were detected by using flow cytometry.The location of IgDR in FLSs was observed by confocal immunofluorescence microscopy.The intrinsic binding affinity of IgD to IgDR on HC-FLSs was observed by fluorescence based receptor binding assay and scatchard analysis.The expression of IgDR on RA-FLSs was analyzed by western blot,the viability of FLSs was measured by CCK-8,and the production of inflammatory cytokines were assessed by inflammation antibody array,after treated with different concentrations of human IgD protein.Results: This study provides firstly that IgDR was constitutively expressed on FLSs,localized in the cell membrane and cytoplasm.The expression of IgDR was higher in RA-FLSs than in HC-FLSs.The equilibrium dissociation constant (KD) measured for IgD-IgDR was 0.067 nM in HC-FLSs.Strikingly,the expression of IgDR on RA-FLSs was stimulated by IgD after 48 h co-culture which analyzed by flow cytometry and western blotting.Simultaneously,IgD could enhance the viability of HC-FLSs and RA-FLSs,and induce IL-1β,IL-6,monocyte chemotactic protein[MCP]-1 and TNF-α production from RA-FLSs,which might attribute to IgD-IgDR cross-linking.Conclusions: These results indicate that IgDR expressed on RA-FLSs which may contribute to activation of FLSs.IgDR represents a potentially novel immunotherapeutic target for the management of RA.