Figure 3.

Multiscale model for PC differentiation. The cellular model (ABM) and molecular GRN (ODE) models are integrated by embedding the GRN in each B-cell and output cell of the ABM. Signals through the BcR (FDC interaction) and CD40 (Tfh interaction) change the state (TF concentrations) of the GRN which is updated at every time step of the ABM. A positively selected CC becomes Ag+ by definition. In scenario 1 simulations an Ag+ cell differentiates to an output cell after asymmetric cell division. In scenario 2, sufficient CD40 signaling may increase BLIMP1 levels to obtain a PC phenotype (BLIMP1+). For precise cell type definitions see Table 2 and Supplementary Figures 6–8, 20 .