A Population Dynamics Model for Clonal Diversity in a Germinal Center

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 divers...

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Bibliographic Details
Main Authors: Mesin, Luka, Victora, Gabriel D., Amitai, Assaf, Kardar, Mehran, Chakraborty, Arup K
Other Authors: Massachusetts Institute of Technology. Institute for Medical Engineering & Science
Format: Article
Published: Frontiers Research Foundation 2017
Online Access:http://hdl.handle.net/1721.1/112995
https://orcid.org/0000-0002-8594-6529
https://orcid.org/0000-0002-1112-5912
https://orcid.org/0000-0003-1268-9602
Description
Summary: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.