In summary, Syk activation was more prominent in FcγRIIb−/− than WT mice, and Syk inhibitors (fostamatinib) effectively attenuated the severity of lupus characteristics (anti-dsDNA levels, proteinuria, and renal histology) in FcγRIIb−/− mice. Here, FCGR2B is linked to systemic lupus erythematosus.