Age-dependent decline of B cell-mediated immunity contributes to West Nile virus susceptibility in mice (P6338)

Abstract

Abstract With aging, the ability of the immune system to mount an efficient response declines, leading to the increased susceptibility of elderly individuals to succumb to infectious diseases. West Nile virus (WNV) is an emerging mosquito-borne flavivirus that causes fatal encephalitis in several vertebrate animals including humans. Despite similar infection rates across all ages, elderly individuals have a higher rate of WNV associated encephalitis and death, and similar results have been documented in laboratory mice. While defects in T cells have been implicated in increased WNV disease severity in aged mice, the contribution of B cell-mediated immune responses has not been addressed. In this study, we compared the immunological response in adult and old mice infected with WNV. We discovered that during the acute phase post infection old mice have delayed germinal center responses that include reduced number of T follicular helper cells and fewer activated germinal center B cells. Consequently, aged mice develop a blunted humoral response with lower serum antibody titers, altered epitope specificity, and reduced serum neutralization. These findings support a model in which decreased B cell-mediated immune responses in elderly animals failed to control viral replication at early times post infection, which resulted in rapid dissemination to the central nervous system, encephalitis, and death.