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Nature Immunology 10, 889–898 (1 August 2009) | doi:10.1038/ni.1748

Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell|[ndash]|stimulating programs in basophils

Kang Chen , Weifeng Xu , Melanie Wilson , Bing He , Norman W Miller , Eva Bengt|[eacute]|n , 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

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.