title: B lymphocytes secrete antigen-presenting vesicles.
abstract: Antigen-presenting cells contain a specialized late endocytic compartment, MIIC (major histocompatibility complex [MHC] class II-enriched compartment), that harbors newly synthesized MHC class II molecules in transit to the plasma membrane. MIICs have a limiting membrane enclosing characteristic internal membrane vesicles. Both the limiting membrane and the internal vesicles contain MHC class II. In this study on B lymphoblastoid cells, we demonstrate by immunoelectron microscopy that the limiting membrane of MIICs can fuse directly with the plasma membrane, resulting in release from the cells of internal MHC class II-containing vesicles. These secreted vesicles, named exosomes, were isolated from the cell culture media by differential centrifugation followed by flotation on sucrose density gradients. The overall surface protein composition of exosomes differed significantly from that of the plasma membrane. Exosome-bound MHC class II was in a compact, peptide-bound conformation. Metabolically labeled MHC class II was released into the extracellular medium with relatively slow kinetics, 10 +/- 4% in 24 h, indicating that direct fusion of MIICs with the plasma membrane is not the major pathway by which MHC class II reaches the plasma membrane. Exosomes derived from both human and murine B lymphocytes induced antigen-specific MHC class II-restricted T cell responses. These data suggest a role for exosomes in antigen presentation in vivo.
authors.affiliation: Department of Cell Biology, Faculty of Medicine and Institute for Biomembranes, Utrecht University, The Netherlands.
authors.forename: G
authors.initials: G
authors.lastname: Raposo
authors.forename: H W
authors.initials: HW
authors.lastname: Nijman
authors.forename: W
authors.initials: W
authors.lastname: Stoorvogel
authors.forename: R
authors.initials: R
authors.lastname: Liejendekker
authors.forename: C V
authors.initials: CV
authors.lastname: Harding
authors.forename: C J
authors.initials: CJ
authors.lastname: Melief
authors.forename: H J
authors.initials: HJ
authors.lastname: Geuze
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000648:ultrastructure; D001426:Bacterial Proteins; D001710:Biotin / Q000378:metabolism; D002458:Cell Fractionation; D002460:Cell Line; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000276:immunology; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology; D003594:Cytoplasmic Granules / Q000276:immunology* / Q000648:ultrastructure; D004705:Endocytosis; D005089:Exocytosis; D006684:HLA-DR Antigens / Q000096:biosynthesis; D004854:Herpesvirus 4, Human; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D006801:Humans; D008213:Lymphocyte Activation; D008561:Membrane Fusion; D051379:Mice; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; C074119:heat-shock protein 65, Mycobacterium; D001710:Biotin; D018833:Chaperonins