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

Authors	CHEN K. XU Weifeng WILSON Melanie HE Bing MILLER WNorman BENGTÉM Eva EDHOLM Eva-Stina SANTINI Paul A RATH Poonam CHIU April CATTALINI Marco LITZMAN Jiří BUSSEL James B HUANG Bihui MEINI Antonella RIESBECK Kristian CUNNINGHAM-RUNDLES Charlotte PLEBANI Alessandro CERUTTI Andrea
Year of publication	2009
Type	Article in Periodical
Magazine / Source	Nature immunology
MU Faculty or unit	Faculty of Medicine
Citation
Field	Immunology
Keywords	Immunoglobulin D; basophils; cytokine expression
Description	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.