What determines the FDC polarization and GC size in affinity maturation

Abstract

Germinal center (GC) is a particular biological structure produced for affinity maturation in the lymphoid follicle during the T-dependent immune response and is an important component of the humoral immune system. However, the impact of morphological features of the GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC including the appearance of two specific zones: the dark zone(DZ) and the light zone (LZ). We find that the development of light and dark zones in GC serves to maintain an effective competition among different cells and promote affinity maturation. On the other hand, by varying the GC size, a phase transition is discovered, which determines a critical GC volume for best performance in both the stochastic and the deterministic model. This critical volume is determined by the distance between the activated B Cell Receptor(BCR) and the target epitope of the antigen. The conclusion is confirmed in both the 2D and the 3D simulations and explains partly the variability in the GC size. Author summaryGerminal center (GC) is an important component of the humoral immune system, which supports antibody affinity maturation and the generation of immunity memory. However, the impact of special morphological features of the GC on antibody production is not clear. According to the latest biological experiments, we establish a spatiotemporal stochastic model to simulate the whole self-organization process of the GC. We use the mixing index of different B cells to quantitatively describe the polarization in GC. With the increase of the mixing index, the affinity of plasma cells decreases gradually, even GC might collapse. Therefore, the development of light and dark zones in GC serves to maintain effective competition among different cells and promote affinity maturation. On the other hand, by varying the GC volume, a phase transition is discovered, which determines a critical GC volume for best performance in both the stochastic and the deterministic model. This critical volume is determined by the distance between the activated B Cell Receptor (BCR) and the target epitope of antigen. The conclusion is confirmed in both the 2D and the 3D simulations and explains partly the variability in the GC size.