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

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • 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
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Microbiology in the medical area
Original languageEnglish
Pages (from-to)889-U121
JournalNature Immunology
Volume10
Issue number8
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes