B细胞活化因子对鼻息肉中B细胞分化和IgE合成的调节机制

B cell activating factor (BAFF) was regarded as a key molecule involved in autoimmune diseases, which can promote B-cell activation and survival. It has been reported BAFF was significantly upregulated in nasal polyps together with excessive B cell accumuation. Based on our preliminary study, we hypothesized that BAFF may play an important role in the pathogenesis of nasal polyps and concomitant asthma. To address this issue, we plan to examine the expression of BAFF and its related signaling molecules in nasal polyps and to evaluate the relevance between accumulation and activation of B-cell and BAFF to clarify the possible role and regulatory mechanism of B-cell accunulation and IgE production in the formation of nasal polyps and concomitant asthma. Next, by using an in vitro culture model of nasal polyps,we plan to examine the possible regulator of BAFF production in nasal epithelial cells stimulated with inflammatory stimuli. Moreover, by stimulated with recombinant BAFF, we plan to evaluate B-cell activation, apoptosis, activation of related signaling pathways and IgE synthesis as well. Moreover, we try to block it by BAFF monoclonal antibody to further clarify the important role of BAFF in the activation of B-cell and the development of nasal polyps which may be asociated with asthma comorbidity. In doing so, it is possible for us to clarify the mechanism of B-cell differentiation and IgE transformation that regulated by BAFF signaling pathway during the formation of nasal polyps. Our finding therefore may provide the evidence for the possible immunomodulation of nasal polyps.

B细胞活化因子（BAFF）能促进B细胞的活化和生存，被视为参与自身免疫性疾病的关键分子。根据国外研究报道鼻息肉中BAFF表达增高和B细胞浸润增强，同时结合预实验结果，我们假设BAFF和B细胞在鼻息肉的发生、发展过程中可能具有关键作用。本研究拟首先检测BAFF及相关的信号分子在鼻息肉中的表达，评估BAFF与鼻息肉中B细胞聚集和活化的相关性。然后利用鼻息肉离体细胞和组织培养模型，检测炎性信号对鼻黏膜上皮细胞表达BAFF的刺激作用，采用重组的BAFF对鼻息肉组织块进行刺激，观察B细胞的活化、凋亡和相关信号通路的激活以及IgE的产生情况；并尝试用BAFF和B细胞单克隆抗体干预以进一步明确BAFF在B细胞活化和鼻息肉发生及诱发哮喘过程中的重要性。这项研究，有可能阐明与鼻息肉发生过程中BAFF信号通路对B细胞分化和IgE的产生转换的调控机制，为探索可能的免疫调控提供依据。

慢性鼻窦炎鼻息肉尤其是伴发哮喘的鼻息肉发病过程中B细胞稳态及体液免疫失衡机制尚不清楚。结合基础研究发现，B细胞活化因子（BAFF）参与B细胞的活化和生存，但其在鼻息肉发病过程中的可能作用并不清楚。本研究检测了伴和不伴哮喘鼻息肉组织的免疫组织学特点尤其是B细胞浸润相关情况，评估了组织体液免疫应答特点，BAFF表达与B细胞、浆细胞浸润间的相关性。研究发现，通过免疫组化检测组织中B细胞的标记CD20、浆细胞标记CD138的表达情况，证实鼻息肉组织中存在B细胞及浆细胞的高浸润；发现慢性鼻窦炎患者鼻息肉组织中BAFF等较对照鼻黏膜组织明显增高；鼻息肉组织匀浆中BAFF蛋白水平与IgE、IL-5表达水平呈正相关；合并哮喘的鼻息肉患者组织BAFF、IgE及IL-5水平高于非哮喘的慢性鼻窦炎鼻息肉组织；通过免疫组化及流式细胞技术证实鼻息肉组织中同时存在高水平的Bcl6+CD4+Tfh细胞浸润，且与B细胞聚集及活化、嗜酸性浸润、合并哮喘、息肉复发存在关联。这些研究为阐明BAFF及B细胞活化在慢性鼻窦炎鼻息肉发病中的作用，探索更有效的干预靶点提供了基础。