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 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.


CONCLUSIONS
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.


CONCLUSIONS
Our data suggest that exosomes from B lymphocytes are an immunostimulatory factor in allergic immune responses.
Admyre
Charlotte
C
Department of Medicine, Clinical Allergy Research Unit, Karolinska Institutet, Stockholm, Sweden. Charlotte.Admyre@ki.se
Bohle
Barbara
B
Johansson
Sara M
SM
Focke-Tejkl
Margarete
M
Valenta
Rudolf
R
Scheynius
Annika
A
Gabrielsson
Susanne
S
D000485:Allergens / Q000276:immunology* / Q000378:metabolism; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D052179:Antigens, Plant; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D029662:Betula / Q000276:immunology; D002461:Cell Line, Transformed; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D006801:Humans; D010455:Peptides / Q000276:immunology* / Q000378:metabolism; D011058:Pollen / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism; D022161:Transport Vesicles / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D018984:Epitopes, T-Lymphocyte; D010455:Peptides