B Cell Functions in the Development of Type I Allergy and Induction of Immune Tolerance.

Abstract

B cells are key players in the mechanisms underlying allergic sensitization, allergic reactions, and tolerance to allergens. Allergen-specific immune responses are initiated when peptide:MHCII complexes on dendritic cells are recognized by antigen-specific receptors on T cells followed by interactions between costimulatory molecules on the surfaces of B and T cells. In the presence of IL-4, such T-B cell interactions result in clonal expansion and isotype class-switching to IgE in B cells, which will further differentiate into either memory B cells or PCs. Allergic reactions are then triggered upon cross-linking of IgE-FcɛRI complexes on basophils and mast cells, leading to cell degranulation and the release of pro-inflammatory mediators.Mechanisms underlying effective allergen-specific immunotherapy (AIT) involve the induction of Tregs and the secretion of blocking IgG4 antibodies, which together mediate the onset and maintenance of immune tolerance towards non-hazardous environmental antigens. However, the importance of regulatory B cells (Breg) for tolerance induction during AIT has gained more attention lately. Studies in grass pollen- and house dust mite-allergic patients undergoing SCIT reported increased frequencies of IL-10+ Breg cells and a positive correlation between their number and the improvement of clinical symptoms. Thus, Breg are emerging as biomarkers for monitoring tolerance to allergens under natural exposure conditions and during AIT. Further research on the role of other anti-inflammatory cytokines secreted by Breg will help to understand their role in disease development and tolerance induction.