Anamnestic responses induced by antigen persisting on follicular dendritic cells from cyclophosphamide-treated mice

In contrast to most mouse lymph node cells, follicular dendritic cells (FDCs) resist cyclophosphamide (Cy; 300 mg/kg)-mediated destruction in vivo. In this study we sought to determine if antigen-bearing FDCs from Cy-treated animals maintained biological activity. We were especially interested in whether FDCs from Cy-treated animals could stimulate an antibody response when combined with primed spleen cells and whether the FDCs needed to be intact and viable for stimulation to occur. The effect of Cy treatment on lymph node histology, number of T cells and B cells, and the 'spontaneous antibody response' was determined. Cy treatment resulted in a massive depletion of the lymph node cortex and a loss of follicles and germinal centres. Over 90% of B cells in the lymph node were eliminated. The paracortex was more resistant although nearly 80% of T cells were eliminated. Cy treatment also eliminated the 'spontaneous antibody response' as established by in vitro culture or after adoptive transfer. The addition of primed spleen cells to antigen-bearing FDCs including sonicated non-viable FDCs from Cy-treated animals resulted in an anamnestic antibody response. Memory lymphocytes, injected into the hind foot pads of Cy-treated animals, migrated to the follicular area of popliteal lymph nodes and cells from these reconstituted nodes spontaneously responded upon subsequent adoptive transfer. It was concluded that antigen retained on Cy-treated FDCs maintains its immunogenicity and is capable of inducing a 'spontaneous antibody response' or an anamnestic response. Furthermore antigen on FDCs or on fragments of FDCs from one animal can interact with memory cells from another animal to induce a productive antibody response. Lymph nodes enriched for FDCs by Cy treatment should be a good source of FDCs for isolation and further study of the nature of this interaction.