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Shan, Meimei; Carrillo, Jorge; Yeste, Ada; Gutzeit, Cindy; Segura-Garzón, Daniel; Walland, A. Cooper; Pybus, Marc; Grasset, Emilie K.; Yeiser, John R.; Matthews, Dean B.; van de Veen, Willem; Comerma, Laura; He, Bing; Boonpiyathad, Tadech; Lee, Haekyung; Blanco, Julià; Osborne, Lisa C.; Siracusa, Mark C.; Akdis, Mübeccel; Artis, David; Mehandru, Saurabh; Sampson, Hugh A.; Berin, M. Cecilia; Chen, Kang; Cerutti, Andrea
Immunity (Cambridge, Mass.), 10/2018, Volume: 49, Issue: 4Journal Article
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 basophils by interacting with the CD44-binding protein galectin-9. When engaged by antigen, basophil-bound IgD increased basophil secretion 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 center T 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 degranulation induced by IgE co-ligation. Thus, IgD may link B cells with basophils to optimize humoral T helper type 2-mediated immunity against common environmental soluble antigens. Display omitted •IgD interacts with basophils through the CD44-binding protein galectin-9•IgD ligation by antigen elicits basophil release of Th2 cell-associated cytokines•IgD-activated basophils enhance B cell production of IgG1 and IgE•IgD interferes with IgE-mediated basophil degranulation The function of IgD has been mysterious. Shan et al. find that IgD recognized food antigens and targeted basophils through galectin-9. IgD ligation by antigen induced basophil secretion of IL-4, IL-5, and IL-13, which amplified Th2 cell-mediated IgG1 and IgE production by B cells. IgD also constrained IgE-mediated basophil degranulation.
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