From affinity selection to kinetic selection in Germinal Centre modelling
Fig 2
Schematic of Ag collection scenarios.
Three mechanisms of Ag collection based on affinity and kinetic selection. The green rows denote the steps that the scenarios have in common. The starting point of each scenario is the event at which a free CC arrives at an Ag binding site. All scenarios end when the Ag collection phase is finished (last grey row), and the cell can engage in T-cell interactions. When no Ag is collected within 42 minutes, the CC will go into apoptosis. (A) Scenario-0: Competition for Ag depends on affinity directly. The CC’s probability of binding to Ag depends on the local Ag concentration (not shown in the figure) and CC’s affinity. After binding, the Ag extraction always starts directly. CC stays in bond until the Ag extraction process is finished after a period specified by a parameter ’Ag extraction time’ whereafter the CC captures the Ag. Subsequently, the CC may collect more Ag or engage in T-cell interactions. (B) Scenario-1: Competition for Ag collection depends on association (Pa) and dissociation (Pd) probabilities of CC that rely on the affinity. In this scenario, a CC associates to Ags presented on FDCs according to Ag concentration at the binding site and Pa. In the next time step, the bond dissociates with a probability of dissociation (Pd) or otherwise, CC initiates the Ag extraction process. During the Ag extraction process, the bond between CC and Ag still can get disrupted probabilistically (red arrow) at each time-step (dt = 0.002 h) with probability Pd that may lead to disruption of Ag extraction before it is fully complete, in which case the CC dissociates without obtaining Ag. Subsequently, if the bond between CC and Ag does not dissociate due to interruptions during the Ag extraction, CC collects the Ag and re-engages in another interaction. (C) Scenario-2: Similar to Scenario-1, only there are no interruptions after initiation of Ag extraction.