Yu Chengcheng, Jia Han, Yu Yan
Affiliated Hospital, Jilin Medical University, Huashan St. No. 81, Jilin, China.
Stomatology College, Beihua University, Jilin, China.
Odontology. 2025 Jun 2. doi: 10.1007/s10266-025-01124-2.
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.
先前的研究已经证实，记忆B细胞通过产生核因子κB受体活化因子配体（RANKL）促进破骨细胞生成。然而，在牙周炎期间，转换型（CD27 + IgD-）和未转换型（CD27 + IgD +）记忆B细胞的表型和功能改变尚未完全明确。本研究旨在阐明未转换型记忆B细胞在牙周炎中的具体作用。我们使用流式细胞术分析了两种记忆B细胞亚群的分布和功能，以评估它们的频率和表型。使用酶联免疫吸附测定（ELISA）和聚合酶链反应（PCR）评估细胞因子RANKL、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的产生。此外，进行细胞培养实验以研究Toll样受体（TLRs）对记忆B细胞产生细胞因子的影响及其诱导破骨细胞生成的能力。我们的研究结果显示，与健康个体相比，牙周炎患者牙龈组织中转换型记忆B细胞的比例更高，未转换型记忆B细胞的比例更低（p < 0.05）。牙周炎症与转换型记忆B细胞中TNF-α mRNA水平升高以及未转换型记忆B细胞中IL-6 mRNA水平升高相关，TLR9和TLR7/8在这些过程中发挥作用。此外，TLR4增强了记忆B细胞产生RANKL和促进破骨细胞生成的能力。这些结果提示了一种新的机制，即未转换型记忆B细胞在不依赖抗体分泌的情况下促进牙周炎症和牙槽骨吸收，并突出了TLRs在加重牙周炎局部炎症中的潜在作用。
