ONTOGENY AND DIFFERENTIATION OF IGE-B LYMPHOCYTES

IGE-B 淋巴细胞的个体发育和分化

• 批准号: 3480797
• 负责人: KIMISHIGE ISHIZAKA
• 金额: $ 13.13万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1978
• 资助国家: 美国
• 起止时间: 1978-05-01 至 1991-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480797
• 关键词: B lymphocyte; Freund's adjuvant; T lymphocyte; antibody; cell differentiation; helper T lymphocyte; histogenesis; humoral immunity; immune adherence reaction; immunofluorescence technique; immunoglobulin E; immunoglobulin M; immunopathology; immunoregulation; microorganism antigen; monoclonal antibody; radiotracer; suppressor T lymphocyte; tissue /cell culture; ultracentrifugation

Final goal of our research is to regulate the IgE antibody response based on physiological mechanisms of the antibody response. Our previous studies have shown that the IgE antibody response is regulated by T cell factors having affinity for IgE. One of the IgE-binding factors selectively enhances the IgE response (IgE-potentiating factor), while another IgE-binding factor suppresses the response (IgE-suppressive factor). The two IgE-binding factors are glycopeptides which share a common structural gene and differ in their carbohydrate moieties. Evidence was obtained that the same T cells can produce both IgE-potentiating factor and IgE-suppressive factor, and that the nature of IgE-binding factors formed by the cells is decided by two T cell factors; glycosylation enhancing factor (GEF) and glycosylation inhibiting factor (GIF). It became clear that GIF is a fragment of phosphorylated lipomodulin, i.e., a phospholipase inhibitory protein, while GEF is a kallikrein-like enzyme. Specific aims of the current proposal are to determine possible roles of GIF and GEF in the immune responses. i) We shall establish antigen-specific T cell clones and T cell hybridomas which release IgE-suppressive factor upon antigenic stimulation, and determine whether GEF will switch the cells from the formation of IgE-suppressive factor to the formation of IgE-potentiating factor. ii) We shall determine whether carbohydrate moieties in IgG-binding factors may have important role in their biologic activities. iii) Recent experiments have shown that GIF released from antigen-specific suppressor T cells has affinity for antigen and bears I-J determinant(s). We shall characterize antigen-specific GIF, and compare this factor with antigen-specific suppressor factors. iv) We shall determine possible association of I-J determinants with lipomodulin, and investigate effects of anti-lipomodulin and anti-I-J alloantibodies on the IgE antibody responses. v) Our preliminary experiments have shown that GIF is immunosuppressive on the IgE and IgG antibody responses. Thus, we shall investigate mechanisms of immunosuppression. vi) Physicochemical and biochemical activities of GEF will be determined. vii) Since our preliminary experiments suggested that GEF is released from antigen-primed Ly 1+ T cells upon antigenic stimulation, and GEF from this source has affinity for antigen, we shall determine whether "antigen-specific" GEF might have some relationship to antigen-specific augmenting factor. viii) We shall determine possible effects of monoclonal anti-GEF on the IgE antibody formation.

我们研究的最终目标是调节IgE抗体的应答 关于抗体反应的生理机制。我们之前的研究 已经表明，IgE抗体反应受T细胞因子调节 对IgE有亲和力。选择性免疫球蛋白E结合因子之一 增强IgE应答(IgE增强因子)，而另一种 免疫球蛋白结合因子抑制反应(IgE抑制因子)。这个 两种IgE结合因子是具有共同结构的糖肽 基因和不同的碳水化合物部分。有证据表明 同样的T细胞可以同时产生IgE增强因子和 Ig E抑制因子，以及Ig E结合因子的性质形成 由两个T细胞因子决定；糖基化增强 糖化抑制因子(GIF)和糖基化抑制因子(GIF)。事情变得很清楚了 该GIF是一段磷酸化的脂调蛋白，即磷脂酶 抑制蛋白，而全球环境基金是激肽释放酶样酶。 当前提案的具体目标是确定 GIF和全球环境基金在免疫反应中的作用I)我们将建立 抗原特异性T细胞克隆和释放的T细胞杂交瘤 免疫抑制因子对抗原刺激，并确定是否 全球环境基金将细胞从形成IgE抑制因子转换为 免疫球蛋白E增强因子的形成。二)我们将决定是否 免疫球蛋白结合因子中的碳水化合物部分可能在 它们的生物活动。三)最近的实验表明，GIF 从抗原特异性抑制T细胞中释放出来的T细胞与抗原有亲和力 并带有I-J行列式(S)。我们将描述抗原特异性的GIF， 并将该因子与抗原特异性抑制因子进行比较。四)我们 应确定I-J决定因素与脂调节蛋白的可能联系， 并观察抗脂调节蛋白和抗I-J同种异体抗体对血管内皮细胞生长的影响。 免疫球蛋白E抗体反应。五)我们的初步实验表明 GIF对Ig E和Ig G抗体反应有免疫抑制作用。因此，我们 应研究免疫抑制的机制。六)物理化学和 将确定全球环境基金的生化活动。Vii)由于我们的 初步实验表明，全球环境基金是从抗原启动释放出来的 LY-1+T细胞在抗原刺激下，来自该来源的全球环境基金 对于抗原的亲和力，我们将确定是否具有抗原特异性的 可能与抗原特异性扩增因子有关。Viii) 我们将确定单抗对IgE的可能影响。 抗体的形成。