ROLE OF COMPLEMENT RECEPTOR IN THE IMMUNE RESPONSE

补体受体在免疫反应中的作用

• 批准号: 3142475
• 负责人: DOUGLAS T FEARON
• 金额: $ 12.54万
• 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/3142475
• 关键词: B lymphocyte; Epstein Barr virus; T lymphocyte; antiantibody; antibody; autoimmune disorder; autologous transplantation; calcium; cell type; cellular pathology; complement receptor; flow cytometry; 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.

通过补体调节免疫反应可能会通过 C3-和C4衍生的配体与补充的相互作用 淋巴细胞和巨噬细胞的受体。 两个结构相关 结合C3B/C4B和C3DG的补体受体，CRL和CR2， 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 这个项目的目的。 B细胞上CR2的三个功能 已经确定了潜在的增长促进。 第一的， B细胞上的交联CR2和膜IgM引起协同作用 相对于自由细胞内钙浓度的增加 单独使用交联的IgM观察到。仅CR2就没有影响。 CRL也没有单独影响，并且没有协同作用 膜IgM。 提出了研究以确定这一点的基础 CR2和膜IgM之间的相互作用。 其次，预孵育 用C3DG持续24小时的B细胞导致细胞进入S相 用抗IGM刺激后更快。 CR2的作用 在此启动反应中将被定义。 第三，添加C3DG 到无血清培养基的培养基长达四倍的半衰期 B细胞。 在此反应中对CR2进行交联的要求 将被检查。 CRL和CR2的抗原呈递功能 在B细胞上将通过制备荧光素（FL） - C3B，C3BI和C3DG的共轭低聚物。 EBV转化为b 用fl-c3/c4片段脉冲的细胞或fl- 将评估白蛋白作为控制的能力 FL至自体，特异性T细胞系。 具有的T细胞 以这种方式激活其能力 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，在T细胞依赖性，抗原非特异性，多克隆 B细胞激活。