IGE AND IGG SUBCLASS FORMATION

虽然众所周知，引起过敏性疾病的主要原因是 免疫球蛋白E抗体的过度生产及其调控 编队的形成仍然鲜为人知。最近，它在这两个地方都得到了体现 白介素4(IL-4)是辅助性T细胞的产物， 诱导B细胞分泌IgE。此外，IL-4刺激小鼠B细胞 分泌IgG1的细胞，正如我们实验室最近显示的那样，人B 细胞分泌IgG4。然而，人IgE/IgG4的形成机制 体外培养不同于小鼠，目前还不完全 明白了。人B细胞在单个核细胞制剂中，但不是 重组IL-4(rIL-4)与纯化的β细胞共孵育 IgE/IgG4，提示非B细胞群对人类是必要的 RIL-4诱导IgE分泌。此外，我们发现多克隆Beta 细胞激活剂抑制人rIL-4诱导的IgE/IgG4分泌。 IL-4诱导的IgE形成的另一个悬而未决的问题是 变应原与产生IL-4的辅助性T细胞的优先相互作用 对小鼠的初步实验表明，抗原提呈细胞可能 在使辅助性T细胞分化为 IL-4分泌细胞。 拟议研究的目标是围绕三个未解决的问题。 关于IL-4诱导的IgE分泌：1)什么是细胞 人rIL-4体外诱导IgE/IgG4分泌的要求？是什么 抗原提呈细胞在辅助性T细胞分化中的作用 细胞将成为IL-4分泌细胞？3)人类变应原特异性T细胞 细胞克隆能分泌IL-4，但不能分泌IL-2/干扰素-γ？ 具体目标是：1)研究人体对细胞的需求 重组人白细胞介素4体外诱导IgE/IgG4分泌及其特性的研究 对rIL-4有反应的细胞。2)分析其抑制机制。 RIL-4通过β细胞激活剂诱导IgE/IgG4分泌。3)至 确定树突状细胞是否来自不同的解剖结构 PHA反应性小鼠T细胞克隆分化的部位 转化为IL-4或干扰素-γ分泌细胞。4)定量测定IL-1 4、人变应原特异性T细胞克隆产生IL-2和干扰素-γ 并利用变应原特异性T细胞克隆开发出人类多克隆 将变应原偶联至纯化的抗-HBs的β细胞激活系统 人类免疫球蛋白。

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.