Allergen-specific responses of CD19(+)CD5(+)Foxp3(+) regulatory B cells (Bregs) and CD4(+)Foxp3(+) regulatory T cell (Tregs) in immune tolerance of cow milk allergy of late eczematous reactions

Foxp3-expressing cells among CD19(+)CD5(+) B cells were identified as regulatory B cells. Food allergy manifesting as late eczematous reactions is regarded as a non-IgE-mediated food allergy. The diagnosis for milk allergy manifesting as late eczematous reactions was made on the basis of the findings obtained from a double-blind placebo-controlled food challenge in patients with atopic dermatitis. Twelve patients with milk allergy and 12 patients who could tolerate milk were selected. On casein stimulation, the CD19(+)CD5(+)Foxp3(+) B cell (Breg) fraction in CD5(+) B cells decreased from 4.4 ± 1.1% to 3.1 ± 0.7% (P = 0.047, n = 12) in the milk allergy group and increased from 4.4 ± 1.3% to 5.2 ± 1.4% (P = 0.001, n = 10) in the milk-tolerant group. On the other hand, on allergen stimulation, the number of CD4(+)Foxp3(+) regulatory T cells (Tregs) in the milk allergy group and milk-tolerant group increased from 2.6 ± 0.7% to 3.4 ± 0.6% (P = 0.014, n = 9) and from 2.7 ± 1.0% to 3.5 ± 1.0% (P = 0.038, n = 10), respectively. In conclusion, allergen-specific responses of Bregs, rather than those of Tregs, seem to influence the immune responses (i.e., allergy or tolerance) to a food allergen.