Article abstract
Nature Immunology 10, 889 - 898 (2009)
Published online: 28 June 2009 | doi:10.1038/ni.1748
Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell–stimulating programs in basophils
Kang Chen1,2, Weifeng Xu1, Melanie Wilson3, Bing He1, Norman W Miller3, Eva Bengtén3, Eva-Stina Edholm3, Paul A Santini1,2, Poonam Rath1,2, April Chiu1, Marco Cattalini4, Jiri Litzman5, James B Bussel6, Bihui Huang7,2, Antonella Meini4, Kristian Riesbeck8, Charlotte Cunningham-Rundles9, Alessandro Plebani4 & Andrea Cerutti1,2
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.
- Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA.
- Graduate Program of Immunology and Microbial Pathogenesis, Weill Cornell Graduate School of Medical Sciences, New York, New York, USA.
- Department of Microbiology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
- Clinica Pediatrica e Istituto di Medicina Molecolare 'A. Nocivelli', Università di Brescia, Brescia, Italy.
- Department of Clinical Immunology and Allergology, St. Anne's University Hospital, Masaryk University, Brno, Czech Republic.
- Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA.
- Department of Cell and Developmental Biology, Weill Cornell Medical College, New York, New York, USA.
- Medical Microbiology, Department of Laboratory Medicine, Malmö University Hospital, Lund University, Malmö, Sweden.
- Mount Sinai Medical Center, New York, New York, USA.
Correspondence to: Andrea Cerutti1,2 e-mail: acerutti@med.cornell.edu
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