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Follicular dendritic cells (FDC) are only located within follicles of secondary lymphoid tissues. The origin of this peculiar cell type is not clearly defined. To contribute to this study, we applied two monoclonal antibodies (MAS516 and 5B5) considered as specific for fibroblasts to tonsil cryosections and to isolated follicular dendritic cells. On the basis of an enzyme cocktail digestion of human tonsils and a fractionation procedure on albumin gradients, FDC can be prepared in the form of cell aggregates with associated lymphoid cells. MAS516 reacts with surface membrane molecules expressed by human fibroblasts, tissue macrophages and peripheral blood monocytes. With immunoperoxidase assays on tonsil cryosections connective tissue cells and macrophages are stained. Inside germinal centres, heavy labelling of the light zone was found. The MAS516 staining pattern is very similar to that of specific FDC markers DRC-1 or BU10. All isolated FDC reacted with MAS516 antibody. 5B5, considered as a typical fibroblast marker, reacts with human prolyl-4-hydroxylase which is an intracellular enzyme related to collagen biosynthesis. In cryosections, interfollicular and capsular areas showed 5B5 positive connective tissue fibroblasts. In germinal centres, some cells presenting features of FDC were 5B5 positive. After cell separation, 25%-50% of the isolated FDC were labelled with this antibody. This positivity of some FDC for 5B5 antibody may support the idea of their fibroblastic origin. The combination of observations realized in situ and after cell purification ensured an unequivocal recognition and identification of FDC.(ABSTRACT TRUNCATED AT 250 WORDS)

Follicular dendritic cells (FDC) are peculiar cells only located inside lymph follicles and which may be characterized by complex dendritic evaginations retaining high quantities of immune complexes by Fc and C3b receptors. After lipopolysaccharide (LPS) injection in mice the retention of gold-labelled immune complexes was abolished in draining lymph nodes. In order to examine the possibility that the transport of immune complexes to lymph follicles was impaired, we isolated FDC from lymph nodes and incubated them in presence of gold-labelled complexes: no or strongly reduced retention was then observed at the ultrastructural level. This LPS-induced impairment of immune complex fixation by FDC is not due to morphological alteration to the cells but to the inhibition of their Fc and C3b receptors. Further, LPS induces changes in the composition of the lymphocyte population in lymph follicles as higher numbers of blast cells and plasmocytes are observed after treatment.

Follicular dendritic cells (FDC) are located only in lymph follicles and are characterized by their capacity to retain high amounts of immune complexes on their plasma membranes. As their functions in germinal centres are unknown, we isolated them from human tonsils and cultured them with autologous lymphoid cells. Cultures of lymphoid cells alone or with added macrophages were used as controls. Lymphoid cells incorporated tritiated thymidine only when FDC and lectins were added; this could be shown after several periods of time. However, the Ig secretion by lymphoid cell populations was inhibited by FDC after several days in vitro. In contrast, the supernatants of lymphocytes cultured alone or with macrophages only for the same periods of time contained increasing amounts of immunoglobulins. This inhibitory effect of FDC on immunoglobulin production was observed for all considered isotypes. Our data suggest that FDC stimulate lymphoid cell proliferation but reduce B-cell differentiation. This is the first accessory cell activity definitely shown for FDC in cultures.

Follicular dendritic cells isolated from mouse lymph nodes were incubated in the presence of AMP to test 5-nucleotidase (5-Nase) activity. Ultrastructural observations showed the presence of 5-Nase on external membranes but also some activity inside the nucleus. 5-Nase was found associated to Fc receptors labelled with homologous immunoglobulins fixed on colloidal gold particles. Lymphocytes and macrophages, found in association with the follicular dendritic cells, were either 5-Nase positive or negative. The hypothetical roles played by 5-Nase in germinal centers are discussed.

The events occurring inside lymph follicles during a germinal center reaction are poorly understood. Using B and T lymphoid cell populations prepared from human tonsillar lymph follicles, and enriched or not in macrophages or in follicular dendritic cells, we examined the production of cytokines by these cells in vitro. Interleukin 6 (IL-6) and tumor necrosis factor (TNF) were found in the supernatants of cultures stimulated with phytohemagglutinin or pokeweed mitogen. IL-1 beta was occasionally detected; its secretion apparently depends on the origin of the tonsils, the stimulation, and the cell populations. IFN-gamma and IL-2 were not produced in significant amounts by these lymph follicle cells. IL-4 was only found in very low concentrations in the supernatant of the different cell cultures. The cell populations containing follicular dendritic cells produced more IL-6 and TNF than the others, especially than those composed of only B and T cells.