Rate of Immune Complex Cycling in Follicular Dendritic Cells Determines the Extent of Protecting Antigen Integrity and Availability to Germinal Center B Cells

Key Points

• PE-ICs cycle at a time scale of ∼1 h in murine FDCs.

• The trade-off between Ag protection and B cell uptake impacts GCs.

• An in-silico Ag cycling blockade terminated GC reactions.

Visual Abstract

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 Ag. Based on experimental data, we estimated that the average residence time of PE-ICs on FDC surface and interior were 21 and 36 min, respectively. GC simulations show that Ag cycling might impact GC dynamics because of redistribution of Ag on the FDC surface and by protecting Ag from degradation. Ag protection and influence on GC dynamics varied with Ag cycling time and total Ag concentration. Simulations predict that blocking Ag cycling terminates the GC reaction and decreases plasma cell production. Considering that cycling of Ag 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.