A mathematical model on germinal center kinetics andtermination.

We devise a mathematical model to study germinal center (GC) kinetics. Earlier models for GC kinetics areextended by explicitly modeling 1) the cell division history of centroblasts, 2) the Ag uptake by centrocytes,and 3) T cell dynamics. Allowing for T cell kinetics and T-B cell interactions, we study the role of GC Tcells in GC kinetics, GC termination, and B cell selection. We find that GC T cells play a major role in GCformation, but that the maintenance of established GC reactions requires very few T cells only. The resultstherefore suggest that the termination of a GC reaction is largely caused by lack of Ag on the folliculardendritic cells and is hardly influenced by Th cells. Ag consumption by centrocytes is the major factordetermining the decay rate of the antigenic stimulus during a GC reaction. Investigating the effect of the Agdose on GC kinetics, we find that both the total size of the GC and its duration are hardly influenced by theinitial amount of Ag. In the model this is due to a buffering effect by competition for limited T cell helpand/or competition between proliferating centroblasts.