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Title: Mathematical model of broadly reactive plasma cell production

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.

Authors:
 [1];  [2];  [2]
  1. Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
  2. Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States)
Publication Date:
Research Org.:
Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE; National Science Foundation (NSF); Simons Collaboration
OSTI Identifier:
1606751
Grant/Contract Number:  
AC05-00OR22725; 1813011; 524390; 1853495
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Immunology; Mathematics and computing

Citation Formats

Erwin, Samantha, Childs, Lauren M., and Ciupe, Stanca M. Mathematical model of broadly reactive plasma cell production. United States: N. p., 2020. Web. doi:10.1038/s41598-020-60316-8.
Erwin, Samantha, Childs, Lauren M., & Ciupe, Stanca M. Mathematical model of broadly reactive plasma cell production. United States. doi:https://doi.org/10.1038/s41598-020-60316-8
Erwin, Samantha, Childs, Lauren M., and Ciupe, Stanca M. Tue . "Mathematical model of broadly reactive plasma cell production". United States. doi:https://doi.org/10.1038/s41598-020-60316-8. https://www.osti.gov/servlets/purl/1606751.
@article{osti_1606751,
title = {Mathematical model of broadly reactive plasma cell production},
author = {Erwin, Samantha and Childs, Lauren M. and Ciupe, Stanca M.},
abstractNote = {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.},
doi = {10.1038/s41598-020-60316-8},
journal = {Scientific Reports},
number = 1,
volume = 10,
place = {United States},
year = {2020},
month = {3}
}

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