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

Abstract

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 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. 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 = .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. Conclusion 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. Graphical abstract Figure. No Caption available.