Mathematical model of broadly reactive plasma cell production
| dc.contributor.author | Erwin, Samantha | en |
| dc.contributor.author | Childs, Lauren M. | en |
| dc.contributor.author | Ciupe, Stanca M. | en |
| dc.contributor.department | Mathematics | en |
| dc.date.accessioned | 2020-07-29T14:28:13Z | en |
| dc.date.available | 2020-07-29T14:28:13Z | en |
| dc.date.issued | 2020 | en |
| dc.description.abstract | Strain-specific plasma cells are capable of producing neutralizing antibodies that are essential for clearance of challenging pathogens. These neutralizing antibodies also function as a main defense against disease establishment in a host. However, when a rapidly mutating pathogen infects a host, successful control of the invasion requires shifting the production of plasma cells from strain-specific to broadly reactive. In this study, we develop a mathematical model of germinal center dynamics and use it to predict the events that lead to improved breadth of the plasma cell response. We examine scenarios that lead to germinal centers that are composed of B-cells that come from a single strain-specific clone, a single broadly reactive clone or both clones. We find that the initial B-cell clonal composition, T-follicular helper cell signaling, increased rounds of productive somatic hypermutation, and B-cell selection strength are among the mechanisms differentiating between strain-specific and broadly reactive plasma cell production during infections. Understanding the contribution of these factors to emergence of breadth may assist in boosting broadly reactive plasma cells production. | en |
| dc.description.sponsorship | SMC acknowledges funding from National Science Foundation grant No. 1813011. LMC acknowledges support from Simons Collaboration Grant No. 524390 and National Science Foundation grant No. 1853495. We thank the reviewers for the valuable comments and suggestions, which have helped improve the manuscript. This manuscript has been authored by UT-Battelle, LLC under Contract No. DE-AC05-00OR22725 with the U.S. Department of Energy. The United States Government retains and the publisher, by accepting the article for publication, acknowledges that the United States Government retains a non-exclusive, paid-up, irrevocable,worldwide license to publish or reproduce the published form of this manuscript, or allow others to do so, for United States Government purposes. The Department of Energy will provide public access to these results of federally sponsored research in accordance with the DOE Public Access Plan (http://energy.gov/downloads/doe-publicaccess- plan). | en |
| dc.format.mimetype | application/pdf | en |
| dc.identifier.doi | https://doi.org/10.1038/s41598-020-60316-8 | en |
| dc.identifier.uri | http://hdl.handle.net/10919/99452 | en |
| dc.identifier.volume | 10 | en |
| dc.language.iso | en | en |
| dc.publisher | Nature Research | en |
| dc.rights | Creative Commons Attribution 4.0 International | en |
| dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | en |
| dc.title | Mathematical model of broadly reactive plasma cell production | en |
| dc.title.serial | Scientific Reports | en |
| dc.type | Article - Refereed | en |
| dc.type.dcmitype | Text | en |