title: Establishment of murine gammaherpesvirus latency in B cells is not a stochastic event.
abstract: 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.
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Jérémie
authors: J
authors: Decalf
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Cristina
authors: C
authors: Godinho-Silva
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Diana
authors: D
authors: Fontinha
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: Sofia
authors: S
authors: Marques
authors: Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors: J Pedro
authors: JP
authors: Simas
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006566:Herpesviridae Infections / Q000276:immunology* / Q000821:virology; D007111:Immunity, Cellular; D007114:Immunization; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009113:Muramidase / Q000276:immunology*; D018144:Rhadinovirus / Q000472:pathogenicity; D014412:Tumor Virus Infections / Q000276:immunology* / Q000821:virology; D017735:Virus Latency / Q000276:immunology*
chemical_list: C421864:hen egg lysozyme; D009113:Muramidase