ONTOGENY AND DIFFERENTIATION OF IGE-B LYMPHOCYTES

IGE-B 淋巴细胞的个体发育和分化

• 批准号: 3480798
• 负责人: KIMISHIGE ISHIZAKA
• 金额: $ 16.45万
• 依托单位: LA JOLLA INSTITUTE FOR IMMUNOLOGY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-12-01 至 1996-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3480798
• 关键词: B lymphocyte; Freund's adjuvant; Nippostrongylus; T lymphocyte; antibody; antibody receptor; binding proteins; cell differentiation; goats; helper T lymphocyte; histogenesis; humoral immunity; immune adherence reaction; immunofluorescence technique; immunoglobulin E; immunoglobulin M; immunopathology; immunoregulation; laboratory rabbit; laboratory rat; microorganism antigen; mitogens; monoclonal antibody; phospholipase inhibitor; radiotracer; receptor binding; suppressor T lymphocyte; tissue /cell culture; tritium; 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抗体反应， 抗体反应的生理机制。 我们以前的研究 已经表明IgE抗体应答受T细胞因子调节 对IgE有亲和力。 其中一种IgE结合因子选择性地 增强IgE反应（IgE增强因子），而另一种 IgE结合因子抑制反应（IgE抑制因子）。 的 两种IgE结合因子是糖肽，它们具有共同的结构 基因和不同的碳水化合物部分。 获得的证据表明， 相同的T细胞可以产生IgE增强因子， IgE抑制因子与IgE结合因子的性质有关 由细胞决定是由两种T细胞因子决定的;糖基化增强 糖基化抑制因子（GIF）。 很明显 GIF是磷酸化脂调节蛋白的片段，即，磷脂酶 抑制蛋白，而GEF是激肽释放酶样酶。 本提案的具体目标是确定以下方面可能发挥的作用： 免疫反应中的GIF和GEF。 （一）我们将建立 抗原特异性T细胞克隆和T细胞杂交瘤， IgE抑制因子，并确定是否 GEF将使细胞从形成IgE抑制因子转变为 IgE增强因子的形成。 （二）确定是否 IgG结合因子中的碳水化合物部分可能在 他们的生物活动。 最近的实验表明，GIF 从抗原特异性抑制性T细胞释放的对抗原具有亲和力 并带有I-J行列式。 我们将描述抗原特异性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决定簇与脂调节素的可能关联， 并研究抗脂调节蛋白和抗I-J同种抗体对 IgE抗体反应。 （五）我们的初步实验表明， GIF对IgE和IgG抗体应答具有免疫抑制作用。 因此我们 将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物化学活动。 （七）自我们 初步实验表明，GEF是从抗原引发的 Ly 1+ T细胞在抗原刺激后，来自该来源的GEF具有 对于抗原的亲和力，我们将确定是否“抗原特异性”GEF 可能与抗原特异性增强因子有关。 （viii） 我们将确定单克隆抗GEF对IgE的可能影响， 抗体形成。