Rate of immune complex cycling in follicular dendritic cell determines the extent of protecting antigen integrity and availability to germinal center B cells

Abstract

Follicular Dendritic Cells (FDCs) retain immune complexes (ICs) for prolonged time periods and are important for germinal center (GC) reactions. ICs undergo periodic cycling in FDCs, a mechanism supporting an extended half-life of antigen. Based on experimental data we estimated that the average residence time of Phycoerythrin-ICs (PE-ICs) on FDC surface and interior were 21 and 36 minutes, respectively. GC simulations show that antigen cycling might impact GC dynamics due to redistribution of antigen on the FDC surface and by protecting antigen from degradation. Antigen protection and influence on GC dynamics varied with antigen cycling time and total antigen concentration. Simulations predict that blocking antigen cycling terminates the GC reaction and decreases plasma cell production. Considering that cycling of antigen could be a target for the modulation of GC reactions, our findings highlight the importance of understanding the mechanism and regulation of IC cycling in FDCs.