Gregory R Burton Akihiro Masuda Sonya L. Heath Beverly A. Smith John G. Tew Andras K. Szakal Follicular dendritic cells (FDC) in retroviral infection: host/pathogen perspectives Authors' addresses Gngory E Burton', Akihirw Musuda', Sonya L. Heath'. Bv/ttiy A. Smith', John G. Tov', AidiusK. Szakd', 'Department of Micro biology and Immunology, Medical College of Virginia, Virginia Commonwealth Univer.sity Richmond, Virginia, USA. 'Department of Pathology, Tokyo Women's Medical College. Tokyo, Japan. 'Department of Anatomy, Division of Immuno biology. Medical College of Virginia, Virginia Commonwealth Universiiy, Richmond, Virginia, USA. Correspondence to: Gic^ry K Burton Assistant Professor of Microbiology and Immtmology PO, Box 980678 Richmond VA 23298-0678 USA Fax: (804) 828-9946 e-mail: gburton@gems.vcu.edu Acknowledgements This research was supported by grants AI32406, AII7142, T32-AI07407 and AI39963 from the National Institutes of Health and by the Medical College of Virginia, Virginia Commonwealth University HIV/AIDS Center. We also acknowledge reagents supplied by the NIH AIDS Research and Reference Reagent Program. immunological Revrews / 997 Vol. 156: 185-197 Primed in Denmark. All nghts reserved Copyright © Munks^iaard 1997 Immunological Reviews ISSN0105-2896 Summary: Follicular dendritic cells (FDC) are found in the follicles of vir- uiatiy all secondary lymphoid tissues. In health, these cells trap and retain antigens (Ag) in the form of immune complexes and preserve them for months in their native conformation. FDC thus serve as a long-term repos- itory of extracellular Ag important for induction and maintenance of memory responses. In retroviral infection. FDC trap and retain large num- bers of retroviral particles with profound effects on FDC. FDC-trapped ret- rovirus induces follicular hyperplasia, and conventional Ag trapped prior to infection are lost and new Ag cannot be trapped. Concomiiantly, anti- body-forming cells (AFC) specific for Ag lost from FDC decrease followed by loss of specific serum antibody (Ab). Eventually, FDC die and fbllicular lysis occurs. From the pathogen perspective, binding to FDC is remarkably beneficial, bringing together virus and activated target cells that are highly susceptible to infection. Furthermore, FDC permit HIV to infect surround- ing cells even in the presence of a vast excess of neutralizing Ab. Prelimi- nary data suggest tbat FDC maintain virus infectivity - even when the virus cannot replicate. Thus retrovirus infection monopolizes FDC networks, thereby transforming the FDC Ag repository into a highly infectious retro- viral reservoir. Introduction During the 1980s, researchers studying secondary lymphoid tissues from infected individuals observed large amounts ofthe human immunodeficiency virus (HIV) trapped on the den- dritic processes of follicular dendritic cells (FDC) (1-7). Virus trapping results in persistent generalized lymphadenopathy, eventual destruction of FDC and lysis of the lymphoid follicles (5, 8-11). At the same time FDC are destroyed, viral RNA in germinal centers decreases and there is a concomitant increase in circulating levels of infectious virions (12). As FDC are destroyed, lymphoid folhcles involute and generalized immu- nosuppression occurs. The major focus of this review is to examine the consequences of retrovirus association with FDC from the perspective ofthe host and the pathogen, FDC are fotuid in virtually every secondary lymphoid tissue including spleen, lymph node, tonsil and Peyer's patches where they bind Ag-Ab complexes by virtue of receptors for the Fc 185