Benign Autoimmunity in female C57BL/6 mice is intricately linked with Aging and resembles Sjögren’s disease

The C57BL/6 (B6) mouse, used as a non-autoimmune control strain, develops features of autoimmunity at an older age. Here, we investigated how aging affects the dynamics of immune cell populations in salivary glands (SG), an organ targeted in Sjögren’s disease (SjD), usually diagnosed in aged people. Gene expression and immune cell infiltrations in SG were studied in 3-26-month-old female B6 mice. Serum anti-nuclear antibodies were measured to determine systemic autoimmunity. Glandular function was evaluated by pilocarpine-induced salivation. At 8 months, SG showed increased nitrotyrosine+ cells, indicative of elevated oxidative stress, and an upregulated chemokine gene expression. F4/80+ resident macrophages showed heightened CD206 and lowered CD64 expression. Among the increased T and B cell populations in the SG, the presence of age-associated B cells (ABC) was striking. Furthermore, the SG showed preferential recruitment of ABC above the liver or spleen. Over time, the ABC infiltration positively correlated with the frequency of SG Tfh cells. By 14 months, the mice developed lymphocytic foci with germinal center-like structures in SG, similar to those in SjD patients. Despite developing high titers of autoantibodies, the glandular function was unaffected. Our study establishes that aged female B6 mice develop benign autoimmunity targeting the SG. However, the onset of organ dysfunction requires additional factors. This study implies a role for aging SG in SjD pathogenesis.