生发中心是B细胞功能成熟分化为效应性浆细胞和记忆B细胞的场所，对于机体抵抗外界病原感染具有重要作用，同时异常的生发中心反应又会导致自身免疫性疾病或淋巴瘤。申请人早期研究发现滤泡树突状细胞（FDC）对于生发中心B细胞的存活和聚集具有重要作用，然而FDC是如何从分子水平上调节生发中心B细胞反应的还不清楚。本项目将通过转录组测序分析FDC的基因表达谱，寻找生发中心成熟FDC特异性高表达的基因，并研究它们在FDC维持生发中心反应中的作用。我们初步已发现FDC表达的溶血磷脂酶ATX及其产生的溶血磷脂酸LPA在生发中心B细胞反应中有重要作用，我们将会进一步利用细胞生物学手段和基因敲除小鼠模型研究ATX/LPA在生发中心B细胞反应中的具体作用和作用机制，并探索ATX/LPA对B细胞淋巴瘤存活能力的影响。了解FDC调控生发中心B细胞反应的分子机制将会为新型疫苗的设计和B细胞淋巴瘤的诊疗提供新的思路和方法。

Mounting appropriately regulated antibody responses is essential for human health. Germinal center (GC) is the site where B cells undergo rapid proliferation, somatic hypermutation, selection and give rise to high affinity effector cells: plasma cells or memory B cells. Maintenance of normal GC B cells is essential for the quantity and quality of antibody generation, whereas dysregulated GC response could cause autoimmune diseases and lymphoma. Using a short-term cell ablation strategy, we have found that a stroma cell in GC, follicular dendrtitic cell (FDC) is critical for GC B cell survival and clustering. However, the molecular mechanism regarding how FDC regulates GC response is still unclear. Here we propose to isolate FDC, identify specific surface or secreted FDC factors and study the role of these factors in GC B cell response. Initially, we have found that GC FDC expressed ATX, a secreted lysophosphatase D, and its downstream product LPA are critical for GC B cell maintenance. We will further investigate the role of ATX/LPA in GC B cell response. This study is fundamentally important for B cell biology and would provide critical insight on the development of improved vaccines and have the potential to uncover novel therapeutic approaches for GC-derived lymphoma.