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
• 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.