Current model of the initiation of the pathogenesis of Sjögren's syndrome. (1) The disease is triggered by either a virus or hypoestrogenism. (2) Salivary gland epithelial cells (SGECs) become activated and start to express MHC class II molecules. (3) The subsequent activation of plasmacytoid dendritic cells (PDCs) induces a high production of proinflammatory cytokines, including IFNalpha, in individuals with the risk alleles of the susceptibility genes IRF5 and STAT4. (4) Under the influence of the high IFN concentration in the glands, TNF family member B cell-activating factor (BAFF) is produced and, together with the autoantigen presentation on SGECs, stimulates the adaptive immune system.