Phenotypic, transcriptomic, and spatial characterization of CD45RB+ naïve mature B cells: Implications in Sjögren's disease

The conventional classification of mature B cells overlooks the diversity within IgD+ CD27− naïve B cells. Here, to identify distinct mature naïve B cells, we categorized CD45RBMEM55- B cells (NA RB-) and CD45RBMEM55+ B cells (NA RB+) and explore their function and localization in circulation and tissues under physiological and pathological conditions. NA RB+ B cells, found in secondary lymphoid organs, differentiate into plasmablasts and secrete IgM. In Sjögren's disease, their numbers decrease, and they show over-activation and abnormal migration, suggesting an adaptive disease response. NA RB+ B cells also appear in inflamed salivary glands, indicating involvement in local immune responses. These findings highlight the distinct roles of NA RB+ B cells in health and Sjögren's disease. [Display omitted] •.IgD+ CD45RBMEM55+ (NA RB+) and IgD+ CD45RBMEM55- B cells are phenotypically, transcriptionally, and functionally distinct.•NA RB+ B cells normally circulate between lymphoid organs but are recruited to inflamed salivary glands in Sjögren's Disease.•In Sjögren's Disease, NA RB+ B cells show an activated phenotype, altered migration, and are near ectopic lymphoid structures.