How does cytopathicity affect the production of neutralizing antibody?

Abstract

Cytopathic viruses evoke an earlier neutralizing antibody (nAb) response than noncytopathic viruses do. This was previously explained by the elimination of infected B cells by the cytotoxic T cells (CTLs), which predominate during infections with noncytopathic viruses. Using a simple mathematical model we provide a much simpler explanation for this difference in the kinetics of neutralizing antibody production. The analysis of the model shows that the delay in nAb production during infections with noncytopathic viruses is a simple consequence of the cytopathic effect alone: noncytopathic viruses infect a larger fraction of nAb-producing B cells and as a result nAb response is delayed. Extending the model with CTLs, we find that a major effect of CTLs is to limit the antigenic stimulus of the nAb-producing B cells. Thus, by reducing the proliferation rate of nAb-producing B cells, CTLs further delay the production of neutralizing antibodies.