STRUCTURE/FUNCTION OF THE LYMPHOCYTE FCE RECEPTOR

描述(改编自《调查者摘要》)：这是一个续篇 低亲和力受体在研究免疫球蛋白E参与中的应用 (FceRII/CD23)与I型变态反应和炎性细胞因子释放有关。二 已在小鼠CD23基因中发现STAT6位点；其中一个位于 小鼠CD23a的启动子区域和CD23b内含子-2的另一个区域 启动子等效区。两个站点在合作中的作用 CD23的上调将被确定。此外，数字的作用 在CD23a启动子中还存在其他的丹结合蛋白基序。 将特别关注小鼠转录因子E3(MTFE3)作为 基因敲除动物没有CD23和NFkB的结构性表达，因为 假定的NFkB位点的破坏已被证明消除了CD23 启动子记者表达。本网站的互动活动 与NFkB的结合将在凝胶移位和超移位分析中确定，并且 IL-4激活NFkB的可能性将被确定。CD23在其中扮演了重要角色 在齐聚和潜在地与IgE相互作用中。这 知识将被用来制备具有完整的 免疫球蛋白结合活性。这样的构造可能代表着一部小说 免疫球蛋白E同型特异性调节方法。B细胞的体外培养 膜CD23已被证明抑制B细胞的生长和免疫球蛋白，尤其是 艾格，制作。一种完全与IgE结合的可溶性载体的研制 这种活性将有助于研究CD23介导的这种效应的机制 更详细地说。对免疫球蛋白生产的分析表明，免疫球蛋白的顺序 对高CD23的敏感性是IgE和IgG1gM，观察到 生殖系转录本未受影响将注意力转移到转换后 B细胞的发育。我们会特别注意 高CD23诱导B细胞凋亡的可能性 在TUNEL或同等检测中进行检测。两种方法的效果比较 将进行寡聚体与单体sCD23构建。最后， 已有证据表明，寡聚体sCD23结构可以诱导 巨噬细胞和巨噬细胞系释放IL-6。结构性的 炎性细胞因子释放所需的CD23的特性 要下定决心。来自这些研究的新知识可能有助于发展 治疗I型变态反应和控制炎症的新疗法 细胞因子的释放。

DESCRIPTION (Adapted from Investigator's abstract): This is a continuation application to study the involvement of the low affinity receptor for IGE (FceRII/CD23) in Type I allergy and inflammatory cytokine release. Two STAT6 sites have been identified in the murine CD23 gene; one in the promoter region of murine CD23a and another in intron-2 in the CD23b promoter equivalent region. The role of the two sites in cooperative upregulation of CD23 will be determined. In addition the role of a number of other DAN-binding protein motifs are present in the CD23a promoter. Special attention will be on murine transcription factor E3 (mTFE3) as knockout animals have no constitutive expression of CD23 and NFkB since destruction of the putative NFkB site has been shown to abrogate CD23 promoter reporter expression. The activity of this site for interaction with NFkB will be determined in gel shift and supershift assays and the potential for IL-4 to activate NFkB will be determined. CD23 plays a role in both oligomerization and potentially in interacting with IgE. This knowledge will be used to prepare oligomeric CD23 chimeras that have full IgE binding activity. Such constructs could potentially represent a novel method for isotype-specific regulation of IgE. Culture of B cells with membrane CD23 has been shown to inhibit B cell growth and Ig, especially IgE, production. Development of a soluble construct with full IgE-binding activity will allow the mechanism of this CD23-mediated effect to be studied in greater detail. Analysis of Ig production suggests that the order of sensitivity to high CD23 is IgE>IgG1>IgM and the observation that levels of germline transcript are not affected directs attention at post-switch development of the B cell. Special attention will be directed at the possibility that high CD23 can induce apoptosis in B cells and this will be examined in TUNEL or equivalent assays. Comparison of the effects of oligomeric vs monomeric sCD23 constructs will be performed. Finally, evidence has been obtained that an oligomeric sCD23 construct can induce IL-6 release from macrophages and macrophage cell lines. The structural characteristics of CD23 required for the inflammatory cytokine release will be determined. New knowledge from these studies may help in the development of new treatments for Type I allergy and for control of inflammatory cytokine release.