Allergen-Specific Responses of CD19high and CD19low B Cells in Non-IgEMediated Food Allergy of Late Eczematous Reactions in Atopic Dermatitis: Presence of IL-17- and IL-32-Producing Regulatory B Cells (Br17 & Br32)

Background: Food allergies are important etiologic factors in atopic dermatitis. CD19 is a B-cell-specific cellsurface molecule, with a critical role in B-cell activation. Recently, B cells showed independent two subpopulations as CD19hi and CD19low. The allergen-specific responses of the CD19high and CD19low B-cell subpopulations were investigated in patients with non-IgE-mediated food allergy. Methods: Five milk-allergic subjects and eight milk-tolerant subjects were selected by a double-blind placebo-controlled food challenge. Peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with casein or ovalbumin and stained with monoclonal antibodies to distinguish the B-cell subsets. Results: After allergen stimulation, CD19high B cells increased in the number and the fraction in PBMCs in the milktolerant group, whereas those remained unchanged in the milk-allergic group. These responses were constant, regardless of the kind of food allergen (milk or egg). The resulting CD19high/CD19low B-cell ratio increased markedly in the milktolerant group after allergen stimulation, but was unchanged in the milk-allergic group. IL-10, IL-17, IL-32 and TGF-β- producing regulatory B cells and Foxp3-expressing regulatory B cells were identified predominantly on CD19 low and CD5(+) B cells. Conclusions: The response of the CD19high B-cell subpopulation to allergen stimulation is decisive for immune tolerance of non-IgE-mediated food allergy in atopic dermatitis. CD19 high and CD5(+) B cells dominantly produce cytokines and express Foxp3. Especially, IL-17 and IL-32 expressing B cells (Br17 & Br32) are present. The exact immunological role of CD19 and cytokines including IL-17 and IL-32 around B cells in immune tolerance requires further investigation.