Abstract
Background
The involvement of B cells in allergen tolerance induction remains largely unexplored. This study investigates the role of B cells in allergen tolerance induction to high-dose allergen exposure, and to compare B cell responses between allergic patients receiving allergen immunotherapy (AIT) and naturally exposed healthy beekeepers before and during the beekeeping season.
Methods
Circulating B cells were characterized by flow cytometry. PLA-specific B cells were identified using dual color staining with fluorescently labeled phospholipase A2 (PLA). Expression of regulatory B cell-associated surface markers, interleukin-10, chemokine receptors and immunoglobulin heavy chain isotypes was measured. Specific and total IgG1, IgG4, IgA and IgE from plasma as well as culture supernatants of PLA-specific cells were measured by ELISA.
Results
Strikingly similar responses were observed in allergic patients and beekeepers after venom exposure. Both groups showed increased frequencies of plasmablasts, PLA-specific memory B cells and IL-10-secreting CD73-CD25+CD71+ BR1-cells. PLA-specific IgG4-switched memory B cells expanded after bee venom exposure. Interestingly, PLA-specific B cells showed increased CCR5 expression after high-dose allergen exposure while CXCR4, CXCR5, CCR6 and CCR7 expression remained unaffected.
Conclusions
This study provides the first detailed characterization of allergen-specific B cells before and after bee venom tolerance induction. The observed B cell responses in both VIT-treated patients and naturally exposed beekeepers suggest a similar functional immunoregulatory role for B cells in allergen tolerance in both groups. These findings can be investigated in other AIT models to determine their potential as biomarkers of early and successful AIT responses.
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