Center for Autoimmune Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Institute of Bioelectronic Medicine, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, USA.
Sci Adv. 2024 Apr 26;10(17):eadn3760. doi: 10.1126/sciadv.adn3760.
Acetylcholine is produced in the spleen in response to vagus nerve activation; however, the effects on antibody production have been largely unexplored. Here, we use a chronic vagus nerve stimulation (VNS) mouse model to study the effect of VNS on T-dependent B cell responses. We observed lower titers of high-affinity IgG and fewer antigen-specific germinal center (GC) B cells. GC B cells from chronic VNS mice exhibited altered mRNA and protein expression suggesting increased apoptosis and impaired plasma cell differentiation. Follicular dendritic cell (FDC) cluster dispersal and altered gene expression suggested poor function. The absence of acetylcholine-producing CD4 T cells diminished these alterations. In vitro studies revealed that α7 and α9 nicotinic acetylcholine receptors (nAChRs) directly regulated B cell production of TNF, a cytokine crucial to FDC clustering. α4 nAChR inhibited coligation of CD19 to the B cell receptor, presumably decreasing B cell survival. Thus, VNS-induced GC impairment can be attributed to distinct effects of nAChRs on B cells.
乙酰胆碱在脾脏中产生以响应迷走神经激活；然而，其对抗体产生的影响在很大程度上尚未得到探索。在这里，我们使用慢性迷走神经刺激 (VNS) 小鼠模型来研究 VNS 对 T 依赖性 B 细胞反应的影响。我们观察到高亲和力 IgG 的滴度较低，抗原特异性生发中心 (GC) B 细胞较少。慢性 VNS 小鼠的 GC B 细胞表现出改变的 mRNA 和蛋白质表达，表明细胞凋亡增加和浆细胞分化受损。滤泡树突状细胞 (FDC) 簇分散和改变的基因表达表明功能不良。缺乏产生乙酰胆碱的 CD4 T 细胞可减轻这些改变。体外研究表明，α7 和 α9 烟碱型乙酰胆碱受体 (nAChR) 直接调节 B 细胞产生 TNF，TNF 是对 FDC 聚类至关重要的细胞因子。α4 nAChR 抑制 CD19 与 B 细胞受体的共交联，可能降低 B 细胞的存活。因此，VNS 诱导的 GC 损伤可归因于 nAChR 对 B 细胞的不同影响。
