B-LYMPHOCYTES SECRETE ANTIGEN-PRESENTING VESICLES

Antigen-presenting cells contain a specialized late endocytic compartm ent, MIIC (major histocompatibility complex [MHC] class II-enriched co mpartment), that harbors newly synthesized MHC class II molecules in t ransit to the plasma membrane. MIICs have a limiting membrane enclosin g characteristic internal membrane vesicles. Both the limiting membran e and the internal vesicles contain MHC class II. In this study on B l ymphoblastoid cells, we demonstrate by immunoelectron miroscopy that t he limiting membrane of MIICs can fuse directly with the plasma membra ne, resulting in release from the cells of internal MHC class II-conta ining vesicles. These secreted vesicles, named exosomes, were isolated from the cell culture media by differential centrifugation followed b y 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 n ot the major pathway by which MHC class II reaches the plasma membrane . Exosomes derived from both human and murine B lymphocytes induced an tigen-specific MHC class II-restricted T cell responses. These data su ggest a role for exosomes in antigen presentation in vivo.