Role of Der p 1-specific B cells in immune tolerance during 2 years of house dust mite-specific immunotherapy

Background: Long-term follow-up of allergen-specific B cells in terms of immunoglobulin isotype expression, plasmablast differentiation, and regulatory B (Breg) cell development during allergen-specific immunotherapy (AIT) has not been reported. Objective: Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients. Methods: B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequencyof IgA-, IgG(1)-and IgG(4)-switchedDer p 1-specificBcells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. Results: Sixteen of 25 patients completed the 2-year study. Eleven responder patients showed a successful response to AIT, as measured by a decrease in symptom-medication scores from 13.23 +/- 0.28 to 2.45 +/- 0.24 (P = .001) and a decrease in skin prick test reactivity to house dust mite from 7.0 +/- 1.3 to 2.7 +/- 0.5 mm (P 5.001). IgG(4) 1 and IgA 1 Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG(4) 1 but not the IgA 1 fraction. The frequency of plasmablasts and IL-10- and/or IL-1RA-producing Breg cells was greater among responders compared with nonresponders after 2 years. The increased frequency of Der p 1-specific IgG4 1 B cells, plasmablasts, and IL-10(+) and dual-positive IL-10 1 IL-1RA 1 Breg cells significantly correlated with improved clinical symptoms over the course of AIT. Conclusion: Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG(4)-expressing Der p 1-specific B cells, plasmablasts, and IL-10(+) and/or IL-1RA 1 Breg cells.