Establishment of Murine Gammaherpesvirus Latency in B Cells Is Not a Stochastic Event

Murid γ-herpesvirus-4 (muhv-4) promotes polyclonal b cell activation and establishes latency in memory b cells via unclear mechanisms. we aimed at exploring whether b cell receptor specificity plays a role in b cell susceptibility to viral latency and how this is related to b cell activation. we first observed that muhv-4-specific b cells represent a minority of the latent population,and to better understand the influence of the virus on non-muhv-4 specific b cells we used the swhel mouse model,which produce hen egg lysozyme (hel)-specific b cells. by tracking hel+ and hel- b cells,we showed that in vivo latency was restricted to hel- b cells while the two populations were equally sensitive to the virus in vitro. moreover,muhv-4 induced two waves of b cell activation. while the first wave was characterized by a general b cell activation,as shown by hel+ and hel- b cells expansion and upregulation of cd69 expression,the second wave was restricted to the hel- population,which acquired germinal center (gc) and plasma cell phenotypes. antigenic stimulation of hel+ b cells led to the development of hel+ gc b cells where latent infection remained undetectable,indicating that muhv-4 does not benefit from acute b cell responses to establish latency in non-virus specific b cells but relies on other mechanisms of the humoral response. these data support a model in which the establishment of latency in b cells by γ-herpesviruses is not stochastic in terms of bcr specificity and is tightly linked to the formation of gcs. © 2014 decalf et al.