ROLE OF ANTIGEN TRANSPORT BY DENDRITIC CELLS IN AGING

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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.