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