Age-associated B cells are long-lasting effectors that restrain reactivation of latent γHV68

Abstract

Age-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.

Age-associated B cells in viral infection

“…Coculturing ABC-like cells from mice with autoimmune experimental hepatitis with CD4 + T cells resulted in impaired T cell proliferation and decreased IFNγ production [ 42 ]. In contrast, our group and others have reported no differences in IFNγ production by T cells between mice with and without ABCs during chronic LCMV and latent γHV68 infections [ 12 , 37 ]. During influenza infection CD11c + B cells localize to the T cell–B cell boundary in the spleen and more efficiently present antigen than follicular B cells [ 11 ].…”

“…Pathogen-specific ABCs persist long term in the spleen ( Fig 1 ) through at least 100 days postinfluenza infection [ 10 ]. ABCs persist at elevated frequency in the spleen during γHV68 latency, at least 150 days postinfection [ 37 ]. ABCs play an important role in the control and clearance of chronic virus infection.…”

Gammaherpesvirus infection drives age-associated B cells toward pathogenicity in EAE and MS

“…This finding indicates that, in the context EAE, ABCs do not appear to be acting as MOG 35–55 APCs. We have also previously shown no difference in CD8 T cells specific to γHV68 during latent infection between Ctrl and KO mice ( 55 ).…”