Critical role of G protein-coupled receptor 40 in B cell response and the pathogenesis of rheumatoid arthritis in mice and patients

Rheumatoid arthritis (RA) is marked by joint damage and inflammation, with B cells playing a key role by generating autoantibodies. This study shows that G protein-coupled receptor 40 (GPR40) deficiency in B cells leads to increased activation, proliferation, antibody production, germinal center formation, and class switch recombination. GPR40 regulates Plcγ2 phosphorylation and intracellular calcium flux downstream of the B cell receptor by binding to the Gαq protein. In GPR40-deficient mice, susceptibility to collagen-induced arthritis was higher. GPR40 agonists showed potential as therapeutic agents, and their reduced expression in patients with RA correlated with disease onset, suggesting GPR40 as a potential therapeutic target and diagnostic marker.