SRA

Although the contribution of B-cell derived autoreactive antibodies to rheumatoid arthritis (RA) has been studied extensively, the autoantibody-independent roles of B cells in the progression of the disease is not well-defined. By utilizing whole transcriptome profiling of human citrulline-specific B cells, we identified diverse inflammatory pathways, cytokines and transcriptional programs that define the biological role of B cells in RA and identify targets for drug intervention. Significantly, we identified the restricted expression of IL15Ra on citrulline-specific B cells and also demonstrated that B cells can express the epidermal growth factor amphiregulin (AREG) under inflammatory conditions. Mechanistically, we demonstrate that AREG has a direct impact on the cellular effectors of RA; it increases the proliferation and invasiveness of RA fibroblast-like synoviocytes (FLS) and synergizes with ACPA to enhance differentiation of osteoclasts. Overall, we present the first comprehensive transcriptome profile of autoreactive B-cell in an autoimmune disease, which can serve as a foundational dataset for studying the multi-faceted roles of B cells in autoimmune diseases Overall design: Whole transcriptome profile of CCP-specific B cells (RA-CCPPOS) with that of CCP-negative B cells (RA-CCPNEG) from the same donor and hemagglutinin-specific (HAPOS) B cells from healthy individuals elicited upon vaccination with seasonal influenza virus