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

Abstract

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. Allergen-specific B-cell responses during 2 years of house dust mite AIT were compared between responder and nonresponder patients. B cells specific for Der p 1 were detected by using the fluorochrome-labeled allergen method. The frequency of IgA-, IgG₁- and IgG₄-switched Der p 1-specific B cells, plasmablasts, and IL-10- and IL-1 receptor antagonist (IL-1RA)-producing Breg cells were investigated and correlated to clinical response to AIT. 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 = .001). IgG₄⁺ and IgA⁺ Der p 1-specific B cells showed a significant increase after AIT, with a significantly greater frequency in responders compared with nonresponders in the IgG₄⁺ but not the IgA⁺ 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⁺ B cells, plasmablasts, and IL-10⁺ and dual-positive IL-10⁺IL-1RA⁺ Breg cells significantly correlated with improved clinical symptoms over the course of AIT. Allergen-specific B cells in patients responding to AIT are characterized by increased numbers of IgA- and IgG₄-expressing Der p 1-specific B cells, plasmablasts, and IL-10⁺ and/or IL-1RA⁺ Breg cells.