Mathematical model of broadly reactive plasma cell production.
Sci Rep
; 10(1): 3935, 2020 03 03.
Article
em En
| MEDLINE
| ID: mdl-32127549
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Plasmócitos
/
Anticorpos Neutralizantes
/
Modelos Teóricos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2020
Tipo de documento:
Article