title: Murid Gammaherpesvirus Latency-Associated Protein M2 Promotes the Formation of Conjugates between Transformed B Lymphoma Cells and T Helper Cells.
abstract: Establishment of persistent infection in memory B cells by murid herpesvirus-4 (MuHV-4) depends on the proliferation of latently infected germinal center B cells, for which T cell help is essential. Whether the virus is capable of modulating B-T helper cell interaction for its own benefit is still unknown. Here, we investigate if the MuHV-4 latency associated M2 protein, which assembles multiprotein complexes with B cell signaling proteins, plays a role. We observed that M2 led to the upregulation of adhesion and co-stimulatory molecules in transduced B cell lines. In an MHC-II restricted OVA peptide-specific system, M2 polarized to the B-T helper contact zone. Furthermore, it promoted B cell polarization, as demonstrated by the increased proximity of the B cell microtubule organizing center to the interface. Consistent with these data, M2 promoted the formation of B-T helper cell conjugates. In an in vitro competition assay, this translated into a competitive advantage, as T cells preferentially conjugated with M2-expressing B cells. However, expression of M2 alone in B cells was not sufficient to lead to T cell activation, as it only occurred in the presence of specific peptide. Taken together, these findings support that M2 promotes the formation of B-T helper cell conjugates. In an in vivo context this may confer a competitive advantage to the infected B cell in acquisition of T cell help and initiation of a germinal center reaction, hence host colonization.
authors.affiliation: Instituto de Medicina Molecular e Instituto de Microbiologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Diana
authors.initials: D
authors.lastname: Fontinha
authors.affiliation: Instituto de Medicina Molecular e Instituto de Microbiologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Filipa B
authors.initials: FB
authors.lastname: Lopes
authors.affiliation: Instituto de Medicina Molecular e Instituto de Microbiologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Sofia
authors.initials: S
authors.lastname: Marques
authors.affiliation: Instituto de Medicina Molecular e Instituto de Microbiologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Alenquer
authors.affiliation: Instituto de Medicina Molecular e Instituto de Microbiologia, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal.
authors.forename: J Pedro
authors.initials: JP
authors.lastname: Simas
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D016764:Cell Polarity; D049109:Cell Proliferation; D054884:Host-Pathogen Interactions; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D018144:Rhadinovirus / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D014764:Viral Proteins / Q000276:immunology*; D017735:Virus Latency
chemical_list: D015815:Cell Adhesion Molecules; C111390:OVA 323-339; D010446:Peptide Fragments; D014764:Viral Proteins; D010047:Ovalbumin