Abstract
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.
Original language | English |
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Article number | 1693 |
Journal | Frontiers in Microbiology |
Volume | 8 |
Issue number | SEP |
DOIs | |
State | Published - 12 Sep 2017 |
Externally published | Yes |
Bibliographical note
Publisher Copyright:© 2017 Amitai, Mesin, Victora, Kardar and Chakraborty.
Funding
Financial support for this work was provided by a grant from the Ragon Institute of MGH, MIT, & Harvard (AC, AA). MK acknowledges support from NSF grant no. DMR-1708280. GV acknowledges support from NIH grant R01 AI119006.
Funders | Funder number |
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National Science Foundation | 1708280 |
National Institutes of Health | R01 AI119006 |
National Sleep Foundation | DMR-1708280 |
Massachusetts General Hospital | |
Massachusetts Institute of Technology | |
Ragon Institute of MGH, MIT and Harvard |
Keywords
- Affinity maturation
- Clonal evolution
- Germinal center reaction
- Modeling and simulations
- Population dynamics