Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils

Nat Immunol. 2009 Aug;10(8):889-98. doi: 10.1038/ni.1748. Epub 2009 Jun 28.


Immunoglobulin D (IgD) is an enigmatic antibody isotype that mature B cells express together with IgM through alternative RNA splicing. Here we report active T cell-dependent and T cell-independent IgM-to-IgD class switching in B cells of the human upper respiratory mucosa. This process required activation-induced cytidine deaminase (AID) and generated local and circulating IgD-producing plasmablasts reactive to respiratory bacteria. Circulating IgD bound to basophils through a calcium-mobilizing receptor that induced antimicrobial, opsonizing, inflammatory and B cell-stimulating factors, including cathelicidin, interleukin 1 (IL-1), IL-4 and B cell-activating factor (BAFF), after IgD crosslinking. By showing dysregulation of IgD class-switched B cells and 'IgD-armed' basophils in autoinflammatory syndromes with periodic fever, our data indicate that IgD orchestrates an ancestral surveillance system at the interface between immunity and inflammation.

Publication types

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

MeSH terms

  • B-Cell Activating Factor / metabolism
  • B-Lymphocytes / immunology*
  • Basophils / immunology*
  • Basophils / metabolism
  • Cathelicidins / metabolism
  • Cell Line
  • Cytidine Deaminase / metabolism
  • Familial Mediterranean Fever / immunology
  • Haemophilus influenzae / growth & development
  • Haemophilus influenzae / physiology
  • Humans
  • Immunoglobulin Class Switching
  • Immunoglobulin D / biosynthesis
  • Immunoglobulin D / immunology*
  • Immunoglobulin M / immunology*
  • Interleukin-1 / metabolism
  • Interleukin-4 / metabolism
  • Mevalonate Kinase Deficiency / immunology
  • Moraxella catarrhalis / growth & development
  • Moraxella catarrhalis / physiology
  • Protein Binding
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / microbiology


  • B-Cell Activating Factor
  • Cathelicidins
  • IL4 protein, human
  • Immunoglobulin D
  • Immunoglobulin M
  • Interleukin-1
  • TNFSF13B protein, human
  • Interleukin-4
  • Cytidine Deaminase