Immunoglobulin D Enhances Antimicrobial Immunity by Activating Basophils

This invention discloses (1) a method to attenuate IgE-induced release of histamine by human basophils, and therefore, treat or prevent allergies using IgD itself or agents targeting the putative IgD receptor; (2) a method to generate antimicrobial agents by activating basophils with IgD and to screen novel antimicrobial agents from IgD-activated basophils; and (3) a method to produce IgD in vitro.

Technical Merits

Humans produce five classes of immunoglobulins (Igs) known as IgM, IgD, IgG, IgA and IgE. While the functions of IgM, IgG, IgA and IgE are relatively well understood, the function of IgD remains unknown. This is particularly true for soluble IgD, which is secreted by a poorly characterized subset of human B cells. The inventors discovered new functions for immunoglobulin D (IgD). They found that IgD cross-linking profoundly attenuates IgE-induced release of histamine by human basophils, indicating that IgD activates a basophil receptor with IgE-inhibitory properties. They also found that IgD shows strong reactivity for commensal and pathogenic respiratory bacteria and interacts with circulating basophils through a calcium-fluxing receptor different from canonical Fc receptors for IgG, IgA and IgE isotypes. In the presence of specific cross-linking agents such as a bead-conjugated anti-IgD monoclonal antibody, basophils up-regulate the production and release of antimicrobial, opsonizing, inflammatory and antibody-inducing factors, including cathelicidin, interleukin-1 (IL-2), IL-4, IL-13 and BAFF.

Potential Applications

Despite fairly good knowledge about the various steps in the allergic reaction, the prevalence of allergic diseases is still increasing. In some areas of the industrialized world up to 50% of the population is affected. Cornell's invention can be used to:

• Develop non anti-histamine allergy drugs
• Potential for preventing IgE sensitization
• Screening for novel antimicrobial agents