B-Cell Landscape in Inflamed Dental Pulp Reveals Potential Autoimmune Involvement

Dynamic immune responses are evident during the development of pulpitis. However, the cellular and molecular characterization of B cells in this context has long been neglected. This study investigates pulpitis through the lens of B-cell involvement, combining single-cell RNA sequencing with histopathological analysis to generate a comprehensive cellular atlas of healthy and inflamed dental pulp. Our findings reveal a near absence of B/plasma cells in healthy pulp but a marked increase during inflammation. These cells display active antigen presentation and immunoglobulin secretion. In the mouse pulpitis model, B-cell depletion alleviated pulpal inflammation, highlighting the proinflammatory role of B cells. Subclustering analysis identified 4 transcriptionally distinct B-cell subsets, which were validated at the protein level through multiplex immunofluorescence and flow cytometry. Among these, transitional B cells exhibited a noticeable breakdown of tolerance, suggesting a propensity for autoreactivity. Elevated autoantibodies were detected in both tissue samples and isolated plasma cells. Finally, Mendelian randomization analyses and serological assays in mice indicated potential local-systemic interactions in pulpitis. These findings reveal that B cells may contribute to both the local pathology and systemic immunological characteristics of pulpitis, providing a novel perspective on its pathogenesis through potential autoimmune mechanisms.