Immunity
Volume 49, Issue 4, 16 October 2018, Pages 709-724.e8
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Article
Secreted IgD Amplifies Humoral T Helper 2 Cell Responses by Binding Basophils via Galectin-9 and CD44

https://doi.org/10.1016/j.immuni.2018.08.013Get rights and content
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Highlights

  • 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

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 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.

Keywords

B cell
basophil
humoral immunity
IgD
antibody
galectin
Th2
CD44
allergy
mucosal immunity

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14

These authors contributed equally

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These authors contributed equally

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