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

TNF拮抗剂和B细胞消耗疗法（BCDT）治疗类风湿性关节炎（RA）的疗效从根本上改变了病理生理范式，并提出了有关疾病机制的新问题。TNF和B细胞都具有核心重要性，这一观察结果有力地推动了我们对TNF过量产生与B细胞介导的炎症途径之间关系的理解，特别是在疾病发作和治疗反应不足方面。tnf -转基因（TNF-tg）小鼠品系是唯一具有临床证实的RA病因的慢性进展性模型，因此对解决RA的细胞和免疫事件具有宝贵的价值。我们已经开发了一系列新颖的小动物成像方法，包括对比增强（CE） MRI，体内微ct和近红外吲哚花青素绿（NIR-ICG）淋巴流分析，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病前和发病期间，腘窝引流淋巴结（PLN）以可预测的时间顺序发生了巨大变化。在膝滑膜炎之前，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