ROLE OF COMPLEMENT RECEPTOR IN THE IMMUNE RESPONSE

补体受体在免疫反应中的作用

• 批准号: 3142478
• 负责人: DOUGLAS T FEARON
• 金额: $ 14.19万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-30 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3142478
• 关键词: B lymphocyte; Epstein Barr virus; T lymphocyte; antiantibody; antibody; autoimmune disorder; autologous transplantation; calcium; cell type; cellular immunity; cellular pathology; complement receptor; flow cytometry; fluoresceins; guinea pigs; immunoglobulin M; leukocyte activation /transformation; ligands; macrophage; membrane proteins; monoclonal antibody; phorbols; radiotracer; tissue /cell culture; tumor necrosis factor alpha; viral carcinogenesis

Modulation of the immune response by complement may occur through the interaction of C3- and C4-derived ligands with complement receptors on lymphocytes and macrophages. Two structurally related complement receptors, CRl and CR2, that bind C3b/C4b and C3dg, respectively, are present on B lymphocytes. Analysis of their role in proliferative and antigen-presenting reactions of B cells is the aim of this project. Three functions of CR2 on B cells that are potentially growth promoting have been identified. First, crosslinking CR2 and membrane IgM on B cells caused a synergistic increase in free intracellular calcium concentration relative to that observed with crosslinking IgM alone; CR2 alone had no affect. CRl also was without affect alone and did not synergize with membrane IgM. Studies are proposed to determine the basis for this interaction between CR2 and membrane IgM. Second, preincubation of B cells with C3dg for 24 hr caused the cells to enter S phase more rapidly following stimulation with anti-IgM. The role of CR2 in this priming reaction will be defined. Third, addition of C3dg to serum-free culture medium prolonged by four-fold the half-life of B cells. The requirement for crosslinking CR2 in this reaction will be examined. The antigen-presenting functions of CRl and CR2 on B cells will be analyzed by preparing fluorescein (FL)- conjugated oligomers of C3b, C3bi, and C3dg. EBV-transformed B cells that have been pulsed with the FL-C3/C4 fragments or with FL- albumin as a control will be assessed for their capacity to present FL to autologous, FL-specific T cell lines. The T cells that have been activated in this manner will be examined for their capacity to activate reciprocally the antigen-presenting B cell. Demonstration of these reactions would provide a model that describes a role for complement in antigen-specific activation of T cells, and in T cell-dependent, antigen-non-specific, polyclonal B cell activation.

补体对免疫反应的调节可能通过以下方式发生： C3 和 C4 衍生配体与补体的相互作用 淋巴细胞和巨噬细胞上的受体。 两个结构相关 补体受体CRl和CR2，其结合C3b/C4b和C3dg， 分别存在于B淋巴细胞上。 分析他们的角色 在 B 细胞的增殖和抗原呈递反应中 该项目的目标。 CR2 对 B 细胞的三个功能是 已确定潜在的生长促进作用。 第一的， B 细胞上的 CR2 和膜 IgM 交联引起协同作用 细胞内游离钙浓度相对于 单独使用交联 IgM 观察到的结果；单独的 CR2 没有影响。 CR1单独使用也没有影响并且不与 膜 IgM。 建议进行研究以确定这一点的基础 CR2 和膜 IgM 之间的相互作用。 二、预孵化 B细胞与C3dg作用24小时导致细胞进入S期 抗 IgM 刺激后速度更快。 CR2的作用 在此引发反应中将被定义。 三、C3dg的添加 无血清培养基半衰期延长四倍 B 细胞。 该反应中交联CR2的要求 将接受检查。 CR1和CR2的抗原呈递功能 将通过制备荧光素 (FL) 来分析 B 细胞上的变化 - C3b、C3bi 和 C3dg 的共轭寡聚物。 EBV转化B 已用 FL-C3/C4 片段或 FL- 脉冲的细胞 作为对照的白蛋白将评估其呈现的能力 FL 为自体 FL 特异性 T 细胞系。 T 细胞具有 以这种方式激活的设备将被检查其容量 相互激活抗原呈递 B 细胞。 这些反应的演示将提供一个模型 描述了补体在抗原特异性激活中的作用 T 细胞，以及 T 细胞依赖性、抗原非特异性、多克隆 B细胞激活。