IGE AND IGG SUBCLASS FORMATION

虽然众所周知，过敏性疾病的主要原因是过敏性疾病。 IgE抗体的过度产生，IgE抗体的调节 对形成仍然知之甚少。最近，它在两个 小鼠和人白细胞介素-4（IL-4），一种T辅助细胞产物， 诱导B细胞分泌IgE。另外，IL-4刺激鼠B 细胞分泌IgG 1，最近在我们的实验室中显示，人B 细胞分泌IgG 4。然而，人IgE/IgG 4形成的机制 在体外与在小鼠中不同，并且目前还不完全 明白单核细胞制剂中的人B细胞， 用重组IL-4（IL-4）分泌物孵育的纯化β细胞 IgE/IgG 4，表明非B细胞群体是人类免疫所必需的。 rIL-4诱导IgE分泌。此外，我们发现多克隆β-内酰胺酶 细胞活化剂抑制人rIL-4诱导的IgE/IgG 4分泌。 IL-4诱导IgE形成的另一个未解决的问题是 变应原与产生IL-4的T辅助细胞的优先相互作用。 小鼠的初步实验表明，抗原呈递细胞可能 在导致T辅助细胞分化为 IL-4分泌细胞。 本研究的目标是围绕三个开放性问题展开 关于IL-4诱导的IgE分泌：1）什么是细胞 人rIL-4体外诱导IgE/IgG 4分泌的条件？是什么 抗原提呈细胞在辅助性T细胞分化中的作用 细胞成为IL-4分泌细胞？3)人类过敏原特异性T 细胞克隆分泌IL-4但不分泌IL-2/IFN-γ？ 具体目的是：1）研究人体对细胞的需求， rIL-4在体外诱导IgE/IgG 4分泌，并表征β 对rIL-4有反应的细胞。 2)分析其抑制机制， rIL-4通过β细胞活化剂诱导IgE/IgG 4分泌。 3)到 确定树突状细胞是否从不同的解剖结构中获得， 位置引起PHA应答的鼠T细胞克隆的分化 IL-4或IFN-γ分泌细胞。 4)为了定量IL- 4、过敏原特异性人T细胞克隆的IL-2和IFN-γ产生 并使用过敏原特异性T细胞克隆来开发人多克隆抗体， 通过将过敏原偶联到纯化的抗- 人IgM。

Although it is well known that the major cause of allergic diseases is an overproduction of IgE antibodies, the regulation of IgE antibody formation is still poorly understood. Recently, it has been shown in both mice and man that Interleukin-4 (IL-4), a product of T helper cells, induces B cells to secret IgE. Additionally, IL-4 stimulates murine B cells to secrete IgG1 and, as shown recently in our laboratory, human B cells to secrets IgG4. However, the mechanism of human IgE/IgG4 formation in vitro differs from that in the mouse and is presently not fully understood. Human B cells in mononuclear cell preparations but not purified Beta cells incubated with recombinant IL-4 (riL-4) secrets IgE/IgG4, suggesting that a non-B cell population is necessary for human rIL-4 induced IgE secretion. In addition, we found that polyclonal Beta cell activators inhibit the human rIL-4 induced IgE/IgG4 secretion. Another unresolved issue in Il-4 induced IgE formation is the preferential interaction of allergens with IL-4 producing T helper cells. Preliminary experiments in mice suggest that antigen presenting cells may play an important role in causing T helper cells to differentiate into IL-4 secreting cells. The goal of the proposed research is centered on three open questions regarding IL-4 induced IgE secretion: 1) What are the cellular requirements for human rIL-4 induced IgE/IgG4 secretion in vitro? What is the role of antigen-presenting cells in the differentiation of T helper cells to become IL-4 secreting cells? 3) Do human allergen specific T cell clones secrete IL-4 but not IL-2/IFN-gamma? The specific aims are: 1) to study the cellular requirement for human rIL-4 induced IgE/IgG4 secretion in vitro and to characterize the Beta cells responding to rIL-4. 2) To analyze the mechanism of suppression of rIL-4 induced IgE/IgG4 secretion by Beta cell activators. 3) To determine whether dendritic cells obtained from different anatomic locations cause differentiation of PHA-responsive murine T cell clones into either IL-4 or IFN-gamma secreting cells. 4) To quantitate the IL- 4, IL-2 and IFN-gamma production by allergen-specific human T cell clones and to use allergen specific T cell clones to develop a human polyclonal Beta cell activation system by coupling the allergen to purified anti- human IgM.