Toll-like receptor engaged in activation and osteoimmuno-cytokines production by unswitched memory B cells during periodontitis.

Previous research has established that memory B cells contribute to osteoclastogenesis by producing RANKL. However, the phenotypic and functional alterations of switched (CD27 + IgD-) and unswitched (CD27 + IgD +) memory B cells during periodontitis were not fully understood. This study aims to elucidate the specific role of unswitched memory B cells in periodontitis. We analyzed the distribution and function of both memory B cell subsets using flow cytometry to assess their frequency and phenotype. The production of cytokines RANKL, TNF-α, and IL-6 was evaluated using ELISA and PCR. Additionally, cell culture experiments were performed to investigate the impact of TLRs on cytokine production by memory B cells and their capacity to induce osteoclastogenesis. Our findings revealed a higher proportion of switched memory B cells and a lower proportion of unswitched memory B cells in the gingival tissues of periodontitis patients compared to healthy individuals (p < 0.05). Periodontal inflammation was associated with increased TNF-α mRNA levels in switched memory B cells and elevated IL-6 mRNA levels in unswitched memory B cells, with TLR9 and TLR7/8 playing roles in these processes. Furthermore, TLR4 enhanced the ability of memory B cells to produce RANKL and promote osteoclastogenesis. These results suggest a novel mechanism by which unswitched memory B cells contribute to periodontal inflammation and alveolar bone resorption, independent of antibody secretion, and highlight the potential role of TLRs in exacerbating local inflammation during periodontitis.