BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that regulates B lymphocyte proliferation and survival. Mice transgenic for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. This study shows that as BAFF Tg mice age, they develop a secondary pathology resembling Sjögren's syndrome (SS), characterized by severe sialadenitis, reduced saliva production, and destruction of submaxillary glands. In humans, SS is associated with elevated BAFF levels and increased BAFF expression in inflamed salivary glands. The study suggests that excessive BAFF signals may lead to autoreactive B cell survival, contributing to SS pathogenesis. BAFF Tg mice show increased B cell infiltration in salivary glands, with a population resembling marginal zone (MZ) B cells. These MZ-like B cells may play a role in tissue damage in SS and other autoimmune diseases. The study also found elevated BAFF levels in SS patients compared to healthy individuals and other autoimmune diseases, suggesting a more significant role of BAFF in SS progression. The findings indicate that altered B cell differentiation and tolerance due to excess BAFF may be central to SS pathogenesis.BAFF (BLyS, TALL-1, THANK, zTNF4) is a member of the TNF superfamily that regulates B lymphocyte proliferation and survival. Mice transgenic for BAFF develop an autoimmune condition similar to systemic lupus erythematosus. This study shows that as BAFF Tg mice age, they develop a secondary pathology resembling Sjögren's syndrome (SS), characterized by severe sialadenitis, reduced saliva production, and destruction of submaxillary glands. In humans, SS is associated with elevated BAFF levels and increased BAFF expression in inflamed salivary glands. The study suggests that excessive BAFF signals may lead to autoreactive B cell survival, contributing to SS pathogenesis. BAFF Tg mice show increased B cell infiltration in salivary glands, with a population resembling marginal zone (MZ) B cells. These MZ-like B cells may play a role in tissue damage in SS and other autoimmune diseases. The study also found elevated BAFF levels in SS patients compared to healthy individuals and other autoimmune diseases, suggesting a more significant role of BAFF in SS progression. The findings indicate that altered B cell differentiation and tolerance due to excess BAFF may be central to SS pathogenesis.