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Optimality of Mutation and Selection in Germinal Centers
The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate t...
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880589/ https://www.ncbi.nlm.nih.gov/pubmed/20532164 http://dx.doi.org/10.1371/journal.pcbi.1000800 |
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author | Zhang, Jingshan Shakhnovich, Eugene I. |
author_facet | Zhang, Jingshan Shakhnovich, Eugene I. |
author_sort | Zhang, Jingshan |
collection | PubMed |
description | The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ∼100-fold affinity improvements, the number of mutations, the hypermutation rate, and the “all or none” phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understanding of the functions of germinal centers. |
format | Text |
id | pubmed-2880589 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28805892010-06-07 Optimality of Mutation and Selection in Germinal Centers Zhang, Jingshan Shakhnovich, Eugene I. PLoS Comput Biol Research Article The population dynamics theory of B cells in a typical germinal center could play an important role in revealing how affinity maturation is achieved. However, the existing models encountered some conflicts with experiments. To resolve these conflicts, we present a coarse-grained model to calculate the B cell population development in affinity maturation, which allows a comprehensive analysis of its parameter space to look for optimal values of mutation rate, selection strength, and initial antibody-antigen binding level that maximize the affinity improvement. With these optimized parameters, the model is compatible with the experimental observations such as the ∼100-fold affinity improvements, the number of mutations, the hypermutation rate, and the “all or none” phenomenon. Moreover, we study the reasons behind the optimal parameters. The optimal mutation rate, in agreement with the hypermutation rate in vivo, results from a tradeoff between accumulating enough beneficial mutations and avoiding too many deleterious or lethal mutations. The optimal selection strength evolves as a balance between the need for affinity improvement and the requirement to pass the population bottleneck. These findings point to the conclusion that germinal centers have been optimized by evolution to generate strong affinity antibodies effectively and rapidly. In addition, we study the enhancement of affinity improvement due to B cell migration between germinal centers. These results could enhance our understanding of the functions of germinal centers. Public Library of Science 2010-06-03 /pmc/articles/PMC2880589/ /pubmed/20532164 http://dx.doi.org/10.1371/journal.pcbi.1000800 Text en Zhang, Shakhnovich. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Zhang, Jingshan Shakhnovich, Eugene I. Optimality of Mutation and Selection in Germinal Centers |
title | Optimality of Mutation and Selection in Germinal Centers |
title_full | Optimality of Mutation and Selection in Germinal Centers |
title_fullStr | Optimality of Mutation and Selection in Germinal Centers |
title_full_unstemmed | Optimality of Mutation and Selection in Germinal Centers |
title_short | Optimality of Mutation and Selection in Germinal Centers |
title_sort | optimality of mutation and selection in germinal centers |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2880589/ https://www.ncbi.nlm.nih.gov/pubmed/20532164 http://dx.doi.org/10.1371/journal.pcbi.1000800 |
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