Cited by 3,546Extracellular vesicles in diseaseCellular transport and secretionImmunotherapy and Immune Responses

B lymphocytes secrete antigen-presenting vesicles.

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Raposo, G, Nijman, H W, Stoorvogel, W, Liejendekker, R, Harding, C V, Melief, C J, Geuze, H J·1996·The Journal of experimental medicine

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.

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Crossref · 10.1084/jem.183.3.1161

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  • Extracellular vesicles are secreted by both normal and cancerous cells as a means of cell-to-cell communication.

    “These vesicles are secreted by both normal cells and cancerous cells as means of cell-to-cell communication [2-5].”

    From Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies (2013) · cites this paper as [2]

    The Results (p. 1165) show that exosomes released by B-cell lines stimulated T cells, supporting a form of cell-to-cell signaling. The Materials and Methods identify the human B-cell lines as EBV-transformed, while the Discussion (p. 1169) reports only preliminary observations of exosomes on physiological immune cells and says their role in vivo remains to be established. The paper does not establish the broad claim that both normal and cancerous cells secrete vesicles as a means of communication. (LLM, conf=0.85)

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Authors
Raposo, G., Nijman, H. W., Stoorvogel, W., Liejendekker, R., Harding, C. V., Melief, C. J., & Geuze, H. J.
Affiliations
Utrecht University (NL)
Venue
The Journal of experimental medicine
Published
1996-03-01
Volume
183
Issue
3
Pages
1161-1172
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
OpenAlex
W2155366992
Cited by
3,546
References
54
Citations by year
2026: 103 · 2025: 189 · 2024: 247 · 2023: 242 · 2022: 242 · 2021: 274 · 2020: 280 · 2019: 210 · 2018: 214 · 2017: 206 · 2016: 177 · 2015: 159 · 2014: 144 · 2013: 107 · 2012: 99
FWCI
9.72
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • Universiteit Utrecht
  • Nederlandse Organisatie voor Wetenschappelijk Onderzoek
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI 35726, R01AI035726)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
exosomes, MHC class II, B cells, vesicle secretion, membrane fusion, antigen presentation, T cell response
MeSH terms
Animals, Antigen-Presenting Cells, Histocompatibility Antigens Class II, B-Lymphocytes, Bacterial Proteins, Biotin, Cell Fractionation, Cell Line, Cell Line, Transformed, Cell Membrane, Cytoplasmic Granules, Endocytosis, Herpesvirus 4, Human, Exocytosis, HLA-DR Antigens, Humans, Lymphocyte Activation, Membrane Fusion, Protein Conformation, Chaperonins, Chaperonin 60, Mice

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