Germinal center dynamics during acute and chronic infection

Samantha Erwin; Stanca M. Ciupe; Samantha Erwin; Stanca M. Ciupe

doi:10.3934/mbe.2017037

Mathematical Biosciences and Engineering

2017, Volume 14, Issue 3: 655-671. doi: 10.3934/mbe.2017037

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Germinal center dynamics during acute and chronic infection

Samantha Erwin ,
Stanca M. Ciupe ^,

460 McBryde Hall, Virginia Tech, Blacksburg, VA 24061, USA

Received: 16 February 2016 Accepted: 12 October 2016 Published: 01 June 2017
MSC : 92, 34

The ability of the immune system to clear pathogens is limited during chronic virus infections where potent long-lived plasma and memory B-cells are produced only after germinal center B-cells undergo many rounds of somatic hypermutations. In this paper, we investigate the mechanisms of germinal center B-cell formation by developing mathematical models for the dynamics of B-cell somatic hypermutations. We use the models to determine how B-cell selection and competition for T follicular helper cells and antigen influences the size and composition of germinal centers in acute and chronic infections. We predict that the T follicular helper cells are a limiting resource in driving large numbers of somatic hypermutations and present possible mechanisms that can revert this limitation in the presence of non-mutating and mutating antigen.
- B cells,
- Tfh cells,
- germinal centers,
- somatic hypermutations,
- mathematical models
Citation: Samantha Erwin, Stanca M. Ciupe. Germinal center dynamics during acute and chronic infection[J]. Mathematical Biosciences and Engineering, 2017, 14(3): 655-671. doi: 10.3934/mbe.2017037

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Abstract

The ability of the immune system to clear pathogens is limited during chronic virus infections where potent long-lived plasma and memory B-cells are produced only after germinal center B-cells undergo many rounds of somatic hypermutations. In this paper, we investigate the mechanisms of germinal center B-cell formation by developing mathematical models for the dynamics of B-cell somatic hypermutations. We use the models to determine how B-cell selection and competition for T follicular helper cells and antigen influences the size and composition of germinal centers in acute and chronic infections. We predict that the T follicular helper cells are a limiting resource in driving large numbers of somatic hypermutations and present possible mechanisms that can revert this limitation in the presence of non-mutating and mutating antigen.

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