ROLE OF ANTIGEN TRANSPORT BY DENDRITIC CELLS IN AGING

树突状细胞抗原运输在衰老中的作用

• 批准号: 3115982
• 负责人: ANDRAS K. SZAKAL
• 金额: $ 8.33万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-30 至 1988-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3115982
• 关键词: B lymphocyte; T lymphocyte; aging; animal old age; antibody formation; antibody specificity; antigen antibody reaction; antigens; body physical characteristic; cell age; cell components; cellular immunity; cytology; dendrites; electron microscopy; humoral immunity; immune complex; immune complex diseases; immunodeficiency; juvenile animal; lymph nodes; lymphocyte; membrane activity; membrane permeability; plaque assay; scanning electron microscopy; spleen; surface antigens

Role of antigen transport by dendritic cells in aging. Follicular dendritic cells (FDCs) are located in the B-cell compartment of lymph nodes and spleens. FDCs are non-phagocytic cells, which on the basis of morphology and surface markers represent unique cells distinct from lymphocytes and macrophages. The function of FDCs which also distinguish them from other leukocytes, including other dendritic cells, is their ability to trap immune complexes on their surface. FDCs retain these immune complexes for long periods of time. These features of FDCs constitute a requirement for the development of B memory cells and the long term maintenance of immunity. The mechanism of antigen trapping involves the transport of antigen from the site of its injection to lymphoid follicles in the lymph node by a group of antigen transporting cells (ATCs). These ATCs are non-phagocytic, dendritic-like cells which carry the immune complexes on their surface. ATCs are thought to represent pre-FDCs or alternatively cells transporting the antigens to FDCs. Data from our laboratories support the concept that antigen persisting on FDCs functions in an antibody feedback system to maintain B cell memory and to regulate serum antibody levels in vivo. Old mice were observed in our laboratories in independent studies to lack the transport of antigen to lymphoid follicles. These observations correlate with reports on the reduced capacity of old mice to maintain B memory and antibody production. To explain this immunological deficit we proposed the hypothesis that in addition to deficits in the T and B cell compartments, at least in part, the deficiencies of the humoral immune system in old mice may be a consequence of the defective antigen transport. To test this hypothesis, we proposed to study the reasons for the defective antigen transport and the role of this defect in the reduced maintenance of B cell memory and antibody production. Specifically, we plan to obtain quantitative cytological and functional data on the observed defects and use this information to attain the long term objective of repairing this immunological deficit. For this we proposed the use of cell transfer models using isolated ATC/FDC populations, for which our laboratory is uniquely qualified, in conjunction with bone marrow precursors and/or T and B cells or their subsets.

树突状细胞抗原转运在衰老中的作用。 滤泡 树突状细胞（FDC）位于淋巴结的B细胞区室中 和脾脏。 FDC是非吞噬细胞，其基于 形态学和表面标记物代表独特的细胞， 淋巴细胞和巨噬细胞。 FDCs的功能也区分 从其他白细胞，包括其他树突状细胞，是他们的 能够将免疫复合物捕获在其表面。 FDCs保留这些 免疫复合物很长时间。 FDCs的这些特点 构成了B存储单元的发展的要求， 长期保持免疫力。 抗原捕获的机制涉及 将抗原从注射部位转运至淋巴细胞 淋巴结中的滤泡通过一组抗原转运细胞 （ATC）。 这些ATC是非吞噬性的树突状细胞，其携带 它们表面的免疫复合物。 ATC被认为代表了 前FDC或可替代地将抗原转运至FDC的细胞。 数据 我们实验室的结果支持了这样一个概念，即抗原在FDC上持续存在， 在抗体反馈系统中起作用，以维持B细胞记忆， 调节体内血清抗体水平。 在我们的实验室里观察了老年小鼠， 实验室在独立的研究，缺乏运输抗原， 淋巴滤泡 这些观察结果与关于 老年小鼠维持B记忆和抗体产生的能力降低。 为了解释这种免疫缺陷，我们提出了一个假设， 除了T和B细胞区室中的缺陷外，至少部分地， 老年小鼠体液免疫系统的缺陷可能是 抗原转运缺陷的结果。 为了验证这个假设， 我们建议研究抗原转运缺陷的原因， 这种缺陷在降低B细胞记忆维持中的作用， 抗体生产。 具体而言，我们计划获得定量 观察到的缺陷的细胞学和功能数据，并使用此 信息，以实现修复这一长期目标， 免疫缺陷 为此，我们建议使用细胞转移 模型使用隔离的ATC/FDC人群，我们的实验室是 唯一合格的，与骨髓前体和/或T和 B细胞或其亚群。