Mathematical model of broadly reactive plasma cell production

Erwin, Samantha; Childs, Lauren M.; Ciupe, Stanca M.

doi:10.1038/s41598-020-60316-8

Title: Mathematical model of broadly reactive plasma cell production

Journal Article · 03 March 2020 · Scientific Reports

DOI: https://doi.org/10.1038/s41598-020-60316-8 · OSTI ID:1606751

Erwin, Samantha ^[1]; Childs, Lauren M. ^[2]; Ciupe, Stanca M. ^[2]

Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)
Virginia Polytechnic Inst. and State Univ. (Virginia Tech), Blacksburg, VA (United States)

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.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE; National Science Foundation (NSF); Simons Collaboration

Grant/Contract Number:: AC05-00OR22725; 1813011; 524390; 1853495

OSTI ID:: 1606751

Journal Information:: Scientific Reports, Vol. 10, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 3 works

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Simulation of B Cell Affinity Maturation Explains Enhanced Antibody Cross-Reactivity Induced by the Polyvalent Malaria Vaccine AMA1 Chaudhury, Sidhartha; Reifman, Jaques; Wallqvist, Anders The Journal of Immunology, Vol. 193, Issue 5 https://doi.org/10.4049/jimmunol.1401054	journal	July 2014
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