Follicular dendritic cells (FDCs) are stromal cells residing in the primary B cell follicles and germinal centers (GCs) of the secondary lymphoid organs. FDCs are specialized for capturing native antigen in the form of immune complexes (ICs) and retain it for a long period of time in a stable form. As the B cell affinity maturation process that occurs in the GCs rely on the antigen uptake of B cells, FDCs are considered critical for supporting the GC reaction by providing ICs to the B cells although other roles of FDCs have also been recognized. Heesters et al., discovered that antigen in FDCs undergo periodic cycling using an ex-vivo culture system and suggested that this mechanism might be the reason behind the enhanced stability of ICs in the FDCs [Heesters et al., Immunity 2013].
To further characterize the antigen cycling in FDCs and understand its potential implications in GC reactions, we estimated the time scale of antigen cycling using the data of Heesters et al., by performing in-silico simulations. Simulations using an agent-based model of GC reaction [Meyer-Hermann 2012, Binder and Meyer-Hermann 2016] modified to incorporate the dynamics of antigen on FDCs suggested that antigen cycling could impact the GC dynamics by redistributing the antigen on FDC surface and by protecting the antigen from degradation. We also found that the dynamics of antigen cycling has an impact on the extent of antigen protection and GC B cell antigen uptake. Consequently, changes in the antigen cycling dynamics can potentially alter the trade-off between antigen protection from degradation and GC B cell antigen uptake. Further, we predicted that blocking antigen cycling can terminate the GC reactions suggesting that antigen cycling could be a therapeutic target for disrupting chronic pathologic GCs. These findings extend our knowledge of antigen cycling in FDCs and suggest a need to better understand the mechanism of antigen cycling to fully exploit the potential therapeutic opportunities.