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

Author

  • Kang Chen
  • Weifeng Xu
  • Melanie Wilson
  • Bing He
  • Norman W. Miller
  • Eva Bengten
  • Eva-Stina Edholm
  • Paul A. Santini
  • Poonam Rath
  • April Chiu
  • Marco Cattalini
  • Jiri Litzman
  • James B. Bussel
  • Bihui Huang
  • Antonella Meini
  • Kristian Riesbeck
  • Charlotte Cunningham-Rundles
  • Alessandro Plebani
  • Andrea Cerutti

Summary, in English

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.

Publishing year

2009

Language

English

Pages

121-889

Publication/Series

Nature Immunology

Volume

10

Issue

8

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Microbiology in the medical area

Status

Published

Research group

  • Clinical Microbiology, Malmö

ISBN/ISSN/Other

  • ISSN: 1529-2908