B cell-derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce TH2-like cytokines

Background: Exosomes are vesicles of 30 to 100 nm produced by inward budding of endosomal compartments and are released by a range of different cell types. Exosomes from antigen-presenting cells carry immunorelevant molecules like MHC class I and II and costimulatory molecules and thus are suggested to have a role in immune modulation. Objective: To investigate the role of antigen-presenting cell derived exosomes in allergen presentation and T-cell stimulation. Methods: Exosomes were isolated from supernatants of B-cell lines derived from patients with birch pollen allergy. The exesomes were characterized with regard to the expression of surface molecules by flow cytometry. Moreover, exosomes were loaded with T-cell-activating peptides from the major birch allergen Bet v 1, and binding was tested with ELISA. Loaded exosomes were used for stimulation of Bet v 1-specific T-cell lines. Cell proliferation and cytokine production were assessed. Results: The exosomes had a phenotype typical of B cell-derived exosomes with expression of MHC, costimulatory molecules like CD86, tetraspanin proteins such as CD81, and CD19. Furthermore, B cell-derived exosomes bound Bet v 1-derived peptides and subsequently induced a dose-dependent T-cell proliferation. In addition to proliferation, T cells synthesized the cytokines IL-5 and IL-13 in response to peptide-loaded exosomes. Conclusion: These results demonstrate for the first time that exosomes isolated from B cells can present allergen-derived peptides and thereby induce T-cell proliferation and T(H)2-like cytokine production. Clinical implications: Our data suggest that exosomes from B lymphocytes are an immunostimulatory factor in allergic immune responses.