B cell–derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce T_H2-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 exosomes 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_H2-like cytokine production.

Clinical implications

Our data suggest that exosomes from B lymphocytes are an immunostimulatory factor in allergic immune responses.

Key words: Exosomes, Bet v 1, allergy, T cells, B cells

Abbreviations used: APC, Antigen-presenting cell, BAL, Bronchoalveolar lavage, CBA, Cytometric bead array, cpm, Counts per minute, DC, Dendritic cell, FITC, Fluorescein isothiocyanate, PE, Phycoerythrin, TCL, T-cell line