Human gingival immune cell atlas unveils the impaired B cell development in aggressive periodontitis

Aggressive periodontitis (AP; Grade C, Stage 3-4) is rapid destructive condition of periodontium triggered by an imbalanced immune reaction with dysbiosis of periodontal pathogens. AP is characterized by extensive tooth loss in early ages due to its severe nature and rapid progression, significantly impacting the affected individual's quality of life. Despite the severity and refractoriness of the disease, the precise pathophysiology of this hyper-reactive phenotype remains unclear. In this study, we dissected the distinct immunological features in AP by establishing the comprehensive human gingival cell atlas on individuals with AP, chronic periodontitis (CP), and healthy controls (HC). Iterative clustering analysis based on the single-cell transcriptome revealed the distinct populations in B and plasma cells upon the periodontal conditions. AP group exhibited a significant rise in B cells including a unique cell cluster dominantly expressing ID3, a key suppressor of plasma cell development. This observation is coordinated with the impaired phenotypes of antibody class switching in AP patients. Remarkably, the secreted IgM gingival crevicular fluid from AP patients exhibited the autoreactivity to gingival tissues, suggesting a potential autoimmune mechanism that involved in AP pathogenesis. These findings highlight distinct immune cell and antibody profiles in AP, providing the insights into the groundwork for personalized monitoring and proactive intervention approaches to mitigate irreversible tissue damage.