Role of B Cells in Synovial Inflammation & LN Remodeling in RA Arthritis

肿瘤坏死因子拮抗剂和B细胞去除疗法(BCDT)治疗类风湿关节炎(RA)的疗效从根本上改变了类风湿关节炎(RA)的病理生理模式，并对其发病机制提出了新的问题。肿瘤坏死因子和B细胞都是核心细胞，这一观察结果为我们更好地理解肿瘤坏死因子过度产生和B细胞介导的炎症途径之间的关系提供了强大的动力，特别是在疾病发作和治疗反应不足方面。肿瘤坏死因子转基因(肿瘤坏死因子-甘油三酯)小鼠品系是唯一一个具有临床证实的病因的类风湿关节炎慢性进展性模型，因此对于研究类风湿关节炎的细胞和免疫学事件具有非常重要的价值。我们开发了一系列新的小动物成像方法，包括对比增强(CE)MRI、活体微型CT和近红外吲哚青绿(NIR-ICG)淋巴流动分析，以纵向研究与关节关节炎进展相关的事件。这些研究的结果，结合组织学和流式细胞术，显示在膝关节疾病发生之前和期间，引流延髓淋巴结(PLN)在可预见的时间序列中发生了戏剧性的变化。在膝关节滑膜炎之前，引流的PLN

The efficacy of TNF antagonists and B cell depletion therapy (BCDT) in rheumatoid arthritis (RA) have fundamentally altered pathophysiologic paradigms and raised new questions about disease mechanisms. The observation that both TNF and B cells are of central importance provides a strong impetus to improve our understanding ofthe relationship between TNF over-production and inflammation pathways mediated by B cells, particularly in regards to disease flares and inadequate treatment response. The TNF-transgenic (TNF-tg) mouse strain is the only chronically progressive model for RA with a clinically proven etiology, and thus invaluable to address the cellular and immunological events in RA. We have developed a series of novel small animal imaging approaches, including contrast enhanced (CE) MRI, in vivo micro-CT and near infrared indocyanin green (NIR-ICG) analysis of lymphatic flow, to study longitudinally the events associated with progression of joint arthritis. The results from these studies, combined with histology and flow cytometry, showed dramatic changes unfolding in a predictable temporal sequence in the draining popliteal lymph-node (PLN) before and during the onset of knee disease. Prior to knee synovitis, the draining PLNs