The dual aspects of IgD in the development of tolerance and the pathogenesis of allergic diseases.

The cell-surface form of IgD is co-expressed with IgM on mature, naïve B cells as B-cell receptors. The secreted IgD antibody (Ab) is found in relatively modest concentrations in the blood and other body fluids as it has a relatively short serum half-life. IgD Abs produced in the upper-respiratory mucosa presumably participate in host defense against pathogens. The allergen-mediated cross-linkage of basophil-bound IgD Ab enhances type 2 cytokine secretion; IgD Ab may also interfere with IgE-mediated basophil degranulation, suggesting dual and opposing roles of IgD Ab in allergen sensitization and the development of allergen immune tolerance. We recently demonstrated that children with egg allergies who avoided all forms of egg have lower ovomucoid-specific IgD and IgG4 Ab levels than those who only partially avoided egg products and that different mechanisms may regulate allergen-specific IgD Ab production compared to allergen-specific IgG4 Ab production. The relationship between antigen-specific IgD Ab levels and the clinical improvement of asthma and food allergies suggests that antigen-specific IgD Ab affects the process of outgrowing allergies. We discuss the possibility that allergen-specific IgD Ab production reflects low-affinity, allergen-specific IgE production as children outgrow a food allergy.