ROLE OF ANTIGEN TRANSPORT BY DENDRITIC CELLS IN AGING

滤泡树突状细胞(FDC)位于B细胞室。 淋巴和脾。FDCs是非吞噬细胞，在此基础上 的形态和表面标记代表了独特的细胞 淋巴细胞和巨噬细胞。FDDC的功能也区分了 它们来自其他白细胞，包括其他树突状细胞，是他们的 将免疫复合体捕获在其表面的能力。金融数据中心保留这些 长时间的免疫复合体。FDDC的这些特点 构成了B存储单元发展的必备条件和长 长期保持豁免权。抗原捕获的机制包括 抗原从注射部位到淋巴组织的运输 一组抗原转运细胞在淋巴结内的滤泡 (ATCS)。这些ATCs是非吞噬的树突状细胞，它携带 它们表面的免疫复合体。ATC被认为代表着 前FDCs或将抗原转运至FDCs的细胞。数据 来自我们实验室的研究人员支持这样一种概念，即抗原在FDCs上持续存在 抗体反馈系统中维持B细胞记忆和 调节体内血清抗体水平。在我们的实验室里观察到了老老鼠 独立研究中的实验室缺乏将抗原输送到 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，我们提出了一种假设，即在 除了T和B细胞隔间的缺陷，至少部分地， 老年小鼠体液免疫系统的缺陷可能是 有缺陷的抗原运输的后果。为了检验这一假设， 我们建议研究抗原转运缺陷的原因，并 这一缺陷在减少B细胞记忆的维持和 抗体的产生。具体地说，我们计划获得量化 关于观察到的缺陷的细胞学和功能数据，并使用此 为实现修复这一长期目标而提供的信息 免疫缺陷。为此，我们建议使用细胞转移 使用隔离ATC/FDC种群的模型，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。

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.