B cell senescence promotes age‐related changes in oral microbiota

In recent years, there has been increasing attention towards understanding the relationship between age‐related alterations in the oral microbiota and age‐associated diseases, with reports emphasizing the significance of maintaining a balanced oral microbiota for host health. However, the precise mechanisms underlying age‐related changes in the oral microbiota remain elusive. We recently reported that cellular senescence of ileal germinal center (GC) B cells, triggered by the persistent presence of commensal bacteria, results in diminished IgA production with aging and subsequent alterations in the gut microbiota. Consequently, we hypothesize that a similar phenomenon may occur in the oral cavity, potentially contributing to age‐related changes in the oral microbiota. Examination of p16‐luc mice, wherein the expression of the senescent cell marker p16INK4a can be visualized, raised under specific pathogen‐free (SPF) or germ‐free (GF) conditions, indicated that, unlike ileal GC B cells, the accumulation of senescent cells in GC B cells of cervical lymph nodes increases with age regardless of the presence of commensal bacteria. Furthermore, longitudinal studies utilizing the same individual mice throughout their lifespan revealed concurrent age‐related alterations in the composition of the oral microbiota and a decline in salivary IgA secretion. Further investigation involving Rag1−/− mice transplanted with B cells from wild‐type or p16INK4a and p21Waf1/Cip1 ‐double knockout mice unveiled that B cell senescence leads to reduced IgA secretion and alteration of the oral microbiota. These findings advance our understanding of the mechanism of age‐associated changes in the oral microbiota and open up possibilities of their control. At a young age, GC B cells induced by oral antigens (bacteria, viruses, etc.) contribute to the secretion of sufficient salivary IgA into the oral cavity, leading to the symbiotic relationship between the host and oral microbiota (left). However, the induction of cellular senescence in the GC B cells by long‐term stimulation of oral antigens with aging leads to a decrease in IgA secretion in saliva, causing age‐related changes in the oral microbiota, which may result in dysbiosis (right).