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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| Format: | Article |
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Frontiers Research Foundation
2017
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| 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 |
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| author | Mesin, Luka Victora, Gabriel D. Amitai, Assaf Kardar, Mehran Chakraborty, Arup K |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Mesin, Luka Victora, Gabriel D. Amitai, Assaf Kardar, Mehran Chakraborty, Arup K |
| author_sort | Mesin, Luka |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:01:34Z |
| format | Article |
| id | mit-1721.1/112995 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T11:01:34Z |
| publishDate | 2017 |
| publisher | Frontiers Research Foundation |
| record_format | dspace |
| spelling | mit-1721.1/1129952022-01-19T13:45:04Z A Population Dynamics Model for Clonal Diversity in a Germinal Center Mesin, Luka Victora, Gabriel D. Amitai, Assaf Kardar, Mehran Chakraborty, Arup K Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Massachusetts Institute of Technology. Department of Physics Amitai, Assaf Kardar, Mehran Chakraborty, Arup K 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. National Science Foundation (U.S.) (Grant DMR-1708280) 2017-12-29T20:25:19Z 2017-12-29T20:25:19Z 2017-09 2017-05 2017-12-29T20:11:36Z Article http://purl.org/eprint/type/JournalArticle 1664-302X http://hdl.handle.net/1721.1/112995 Amitai, Assaf et al. “A Population Dynamics Model for Clonal Diversity in a Germinal Center.” Frontiers in Microbiology 8 (September 2017): 1603 © 2017 Amitai, Mesin, Victora, Kardar and Chakraborty https://orcid.org/0000-0002-8594-6529 https://orcid.org/0000-0002-1112-5912 https://orcid.org/0000-0003-1268-9602 http://dx.doi.org/10.3389/fmicb.2017.01693 Frontiers in Microbiology Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/ application/octet-stream Frontiers Research Foundation |
| spellingShingle | Mesin, Luka Victora, Gabriel D. Amitai, Assaf Kardar, Mehran Chakraborty, Arup K A Population Dynamics Model for Clonal Diversity in a Germinal Center |
| title | A Population Dynamics Model for Clonal Diversity in a Germinal Center |
| title_full | A Population Dynamics Model for Clonal Diversity in a Germinal Center |
| title_fullStr | A Population Dynamics Model for Clonal Diversity in a Germinal Center |
| title_full_unstemmed | A Population Dynamics Model for Clonal Diversity in a Germinal Center |
| title_short | A Population Dynamics Model for Clonal Diversity in a Germinal Center |
| title_sort | population dynamics model for clonal diversity in a germinal center |
| url | 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 |
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