ROLE OF ANTIGEN TRANSPORT BY DENDRITIC CELLS IN AGING

滤泡树突状细胞 (FDC) 位于 B 细胞区室中 淋巴结和脾脏。 FDC 是非吞噬细胞，其基础 形态和表面标记代表了不同于细胞的独特细胞 淋巴细胞和巨噬细胞。 FDC 的功能还区分 它们来自其他白细胞，包括其他树突状细胞，是它们的 将免疫复合物捕获在其表面的能力。 FDC 保留这些 长时间免疫复合物。 FDC 的这些特点 构成B记忆细胞发育和长期发育的要求 长期维持免疫力。 抗原捕获的机制包括 将抗原从注射部位转运至淋巴 淋巴结滤泡由一组抗原转运细胞组成 （ATC）。 这些 ATC 是非吞噬性树突状细胞，携带 其表面的免疫复合物。 ATC 被认为代表 前 FDC 或将抗原转运至 FDC 的细胞。 数据 我们的实验室支持抗原持续存在于 FDC 上的概念 在抗体反馈系统中发挥作用，维持 B 细胞记忆并 调节体内血清抗体水平。 我们观察到老老鼠 独立研究中的实验室缺乏抗原运输 淋巴滤泡。 这些观察结果与有关报告相关 年老小鼠维持 B 记忆和抗体产生的能力下降。 为了解释这种免疫缺陷，我们提出了这样的假设： 除了 T 细胞和 B 细胞区室的缺陷（至少部分）， 年老小鼠体液免疫系统的缺陷可能与 抗原运输缺陷的结果。 为了检验这个假设， 我们建议研究抗原转运缺陷的原因 这种缺陷在 B 细胞记忆维持减少中的作用 抗体的产生。 具体来说，我们计划获得定量的 观察到的缺陷的细胞学和功能数据并使用它 信息以实现修复此问题的长期目标 免疫缺陷。 为此，我们建议使用细胞转移 使用隔离的 ATC/FDC 群体的模型，我们的实验室是 与骨髓前体和/或 T 结合具有独特的资格 B 细胞或其亚群。

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.