Age-associated B cells are critical for the control of latent gammaherpesvirus 68 infection

Abstract

AbstractAge-associated B cells (ABCs; CD19+CD11c+T-bet+) are increased during an array of viral infections, though their role during viral latency is unexplored. Here, we use murine gammaherpesvirus 68 (γHV68), a homolog of Epstein-Barr virus that latently infects B cells, to demonstrate that ABCs are necessary for the effective control of gamma-herpesvirus latency. We observe that ABCs expand in the spleen during acute infection and persist at least 150 days post-infection. During acute and latent infection ABCs secrete IFNγ and TNF. Using a strain of γHV68 that is cleared following acute infection, we show that ABCs persist in the absence of latent virus, though they secrete less IFNγ and TNF. With a fluorescent virus we demonstrate that ABCs are infected with γHV68 at similar rates to other mature B cells. We find that mice without ABCs display defects in anti-viral IgG2a/c antibodies and are less able to maintain γHV68 latency when challenged with heterologous infection. Together, these results indicate that ABCs are a persistent subset during latent viral infection that controls γHV68 reactivation from latency.