title: Exosomes containing glycoprotein 350 released by EBV-transformed B cells selectively target B cells through CD21 and block EBV infection in vitro.
abstract: Exosomes are nano-sized membrane vesicles released from a wide variety of cells, formed in endosomes by inward budding of the endosomal limiting membrane. They have immune stimulatory-, inhibitory-, or tolerance-inducing effects, depending on their cellular origin, which is why they are investigated for use in vaccine and immune therapeutic strategies. In this study, we explored whether exosomes of different origins and functions can selectively target different immune cells in human peripheral blood. Flow cytometry, confocal laser scanning microscopy, and multispectral imaging flow cytometry (ImageStream) revealed that exosomes derived from human monocyte-derived dendritic cells and breast milk preferably associated with monocytes. In contrast, exosomes from an EBV-transformed B cell line (LCL1) preferentially targeted B cells. This was not observed for an EBV(-) B cell line (BJAB). Electron microscopy, size-distribution analysis (NanoSight), and a cord blood transformation assay excluded the presence of virions in our LCL1 exosome preparations. The interaction between LCL1-derived exosomes and peripheral blood B cells could be blocked efficiently by anti-CD21 or anti-gp350, indicating an interaction between CD21 on B cells and the EBV glycoprotein gp350 on exosomes. The targeting of LCL1-derived exosomes through gp350-CD21 interaction strongly inhibited EBV infection in B cells isolated from umbilical cord blood, suggesting a protective role for exosomes in regulating EBV infection. Our finding also suggests that exosome-based vaccines can be engineered for specific B cell targeting by inducing gp350 expression.
authors.affiliation: Clinical Allergy Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Helen
authors.initials: H
authors.lastname: Vallhov
authors.forename: Cindy
authors.initials: C
authors.lastname: Gutzeit
authors.forename: Sara M
authors.initials: SM
authors.lastname: Johansson
authors.forename: Noémi
authors.initials: N
authors.lastname: Nagy
authors.forename: Mandira
authors.initials: M
authors.lastname: Paul
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.forename: Sherree
authors.initials: S
authors.lastname: Friend
authors.forename: Thaddeus C
authors.initials: TC
authors.lastname: George
authors.forename: Eva
authors.initials: E
authors.lastname: Klein
authors.forename: Annika
authors.initials: A
authors.lastname: Scheynius
authors.forename: Susanne
authors.initials: S
authors.lastname: Gabrielsson
mesh_terms: D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000517:prevention & control*; D055354:Exosomes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007774:Lactation; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008895:Milk, Human / Q000276:immunology / Q000378:metabolism / Q000821:virology; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D011485:Protein Binding / Q000276:immunology; D017464:Receptors, Complement 3d / Q000096:biosynthesis / Q000502:physiology*; D014763:Viral Matrix Proteins / Q000378:metabolism*; D015678:Viral Structural Proteins / Q000378:metabolism
chemical_list: C034059:GP 300-350, Epstein-Barr virus; D008562:Membrane Glycoproteins; D017464:Receptors, Complement 3d; D014763:Viral Matrix Proteins; D015678:Viral Structural Proteins