A Population Dynamics Model for Clonal Diversity in a Germinal Center

• Main Authors: Assaf Amitai, Luka Mesin, Gabriel D. Victora, Mehran Kardar, Arup K. Chakraborty
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2017-09-01
• Series: Frontiers in Microbiology
• Subjects: germinal center reaction; population dynamics; modeling and simulations; clonal evolution; affinity maturation
• Online Access: http://journal.frontiersin.org/article/10.3389/fmicb.2017.01693/full

Germinal centers (GCs) are micro-domains where B cells mature to develop high affinity antibodies. Inside a GC, B cells compete for antigen and T cell help, and the successful ones continue to evolve. New experimental results suggest that, under identical conditions, a wide spectrum of clonal diversity is observed in different GCs, and high affinity B cells are not always the ones selected. We use a birth, death and mutation model to study clonal competition in a GC over time. We find that, like all evolutionary processes, diversity loss is inherently stochastic. We study two selection mechanisms, birth-limited and death limited selection. While death limited selection maintains diversity and allows for slow clonal homogenization as affinity increases, birth limited selection results in more rapid takeover of successful clones. Finally, we qualitatively compare our model to experimental observations of clonal selection in mice.