Germinal center dynamics during acute and chronic infection.

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.