Mechanisms of allergen-specific B cell tolerance in children with cow’s milk-oral immunotherapy and natural outgrowth of milk allergy

Antigen-specific memory B cells play a key role in the induction of immune tolerance to food allergens and clinical healing. Here, we characterized the role of allergen-specific B cells in immune tolerance induced by oral allergen-specific immunotherapy (OIT) and natural tolerance that developed in children who spontaneously outgrew cow’s milk allergy. Increased frequency of circulating milk allergen αS1-casein -specific B cells was observed after OIT and natural tolerance (NT). Milk desensitized subjects showed partial acquisition of tolerance phenotypic features induced tolerance, suggesting that desensitization is an earlier stage of tolerance. Immunoregulatory genes such as IL10RA and IGHG4 are significantly upregulated after OIT (desensitized and tolerance) versus NT. Secreted proteins from allergen-specific B cells revealed higher amounts of regulatory cytokines, IL-10 and TGF-β after OIT and NT. Taken together, allergen-specific B cells are essential elements in regulating food allergen tolerance in both OIT-received and naturally-resolved individuals.