IgD Amplifies IgG and IgE Responses to Common Environmental Antigens through a Basophil-Regulated Immune Surveillance Program

B cells thwart antigenic aggressions by secreting immunoglobulin M (IgM), IgG, IgA and IgE. The function of a fifth antibody, IgD, remains enigmatic. By integrating mouse with human studies, we found that a fraction of B cells generated IgD-secreting plasma cells following exposure to soluble food, airborne or skin antigens. Secreted IgD targeted basophils after interacting with galectin-9, a galactose-binding lectin that recognized the proteoglycan CD44. When engaged by antigen, basophil-bound IgD induced secretion of interleukin-4 (IL-4), IL-5 and IL-13, which facilitated T follicular helper type-2 (TH2)-mediated IgG and IgE responses to IgD-targeted antigens. In addition, basophil-bound IgD elicited cytoskeleton changes that attenuated degranulation upon basophil exposure to antigens dually recognized by IgE and IgD. Thus, IgD may link B cells with basophils to optimize TH2 immune surveillance against common environmental antigens.