Germinal Center Structure Evolution and Affinity Maturation.
Dr. Yoram Louzoun, Department of Biology, Princeton University
Steven H. Kleinstein, Department of Computer Science, Princeton University

Germinal center (GC) structure is evolving in parallel with the affinity changes of the B cells composing the germinal center. We study the evolution of GC structure and the interplay between this structure and B cell affinity. The structure of the GC evolves from a uniform distribution of B cells to a well defined two zones structure and back to a uniform distribution within three weeks. During this time the B cell population evolves from multiple low affinity clones to a small number (usually one or two) high affinity clones. We sought to determine whether these experimentally observed features could result from simple rules of interaction along with diffusion, without the need to invoke chemotaxis. To this end, we developed a simulation describing the 3D structure of the GC, the interactions between B cells, T cells and FDC and the specific mutations in GC B cells. We use the simulation to explain the structural evolution of the GC, the evolution in the number of GC B cells, affinity maturation and the selection of a small number of B cell clones. Our simulation shows that one can explain most of the observed features of GC through a combination of spatial inhmogeneity, competition over access to antigen and over access to T cells and B and T cell diffusion.