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.
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.
Footnotes
This work was supported by the European Union’s Horizon 2020 Research and Innovation Programme under Marie Sklodowska-Curie Grant Agreement 765158 (to T.A.).
The online version of this article contains supplemental material.
- Received December 1, 2020.
- Accepted January 22, 2021.
- Copyright © 2021 by The American Association of Immunologists, Inc.
This article is distributed under The American Association of Immunologists, Inc., Reuse Terms and Conditions for Author Choice articles.
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