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

Immunity. 2018 Oct 16;49(4):709-724.e8. doi: 10.1016/j.immuni.2018.08.013. Epub 2018 Oct 2.


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; CD44; IgD; Th2; allergy; antibody; basophil; galectin; humoral immunity; mucosal immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basophils / immunology*
  • Basophils / metabolism
  • Cell Line, Tumor
  • Cells, Cultured
  • Galectins / genetics
  • Galectins / immunology*
  • Galectins / metabolism
  • Gene Expression Profiling / methods
  • Humans
  • Hyaluronan Receptors / genetics
  • Hyaluronan Receptors / immunology*
  • Hyaluronan Receptors / metabolism
  • Immunoglobulin D / immunology*
  • Immunoglobulin D / metabolism
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / immunology
  • Immunoglobulin G / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / immunology
  • Interleukin-4 / metabolism
  • Mice, Inbred BALB C
  • Protein Binding
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism


  • Galectins
  • Hyaluronan Receptors
  • Immunoglobulin D
  • Immunoglobulin G
  • LGALS9 protein, human
  • Interleukin-4
  • Immunoglobulin E