Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44

Summary B cells thwart antigenic aggressions by releasing immunoglobulin M(IgM), IgG, IgA, and IgE, which deploy well-understood effector functions. In contrast, the role of secreted IgD remains mysterious. We found that some B cells generated IgD-secreting plasma cells following early exposure to external soluble antigens such as food proteins. Secreted IgD targeted basophilsby interacting with the CD44-binding protein galectin-9. When engaged by antigen, basophil-bound IgD increased basophilsecretion of interleukin-4(IL-4), IL-5, and IL-13, which facilitated the generation of T follicular helper type 2 cells expressing IL-4. These germinal centerT cells enhanced IgG1 and IgE but not IgG2a and IgG2b responses to the antigen initially recognized by basophil-bound IgD. In addition, IgD ligation by antigen attenuated allergic basophil degranulationinduced by IgE co-ligation. Thus, IgD may link B cells with basophilsto optimize humoral T helper type 2-mediated immunity against common environmental soluble antigens.