title: Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils.
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.
authors: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA.
authors: Kang
authors: K
authors: Chen
authors: Weifeng
authors: W
authors: Xu
authors: Melanie
authors: M
authors: Wilson
authors: Bing
authors: B
authors: He
authors: Norman W
authors: NW
authors: Miller
authors: Eva
authors: E
authors: Bengtén
authors: Eva-Stina
authors: ES
authors: Edholm
authors: Paul A
authors: PA
authors: Santini
authors: Poonam
authors: P
authors: Rath
authors: April
authors: A
authors: Chiu
authors: Marco
authors: M
authors: Cattalini
authors: Jiri
authors: J
authors: Litzman
authors: James
authors: J
authors: B Bussel
authors: Bihui
authors: B
authors: Huang
authors: Antonella
authors: A
authors: Meini
authors: Kristian
authors: K
authors: Riesbeck
authors: Charlotte
authors: C
authors: Cunningham-Rundles
authors: Alessandro
authors: A
authors: Plebani
authors: Andrea
authors: A
authors: Cerutti
mesh_terms: D053264:B-Cell Activating Factor / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D001491:Basophils / Q000276:immunology* / Q000378:metabolism; D054804:Cathelicidins / Q000378:metabolism; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism; D010505:Familial Mediterranean Fever / Q000276:immunology; D006193:Haemophilus influenzae / Q000254:growth & development / Q000502:physiology; D006801:Humans; D017578:Immunoglobulin Class Switching; D007072:Immunoglobulin D / Q000096:biosynthesis / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D007375:Interleukin-1 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D054078:Mevalonate Kinase Deficiency / Q000276:immunology; D001936:Moraxella catarrhalis / Q000254:growth & development / Q000502:physiology; D011485:Protein Binding; D020545:Respiratory Mucosa / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology
chemical_list: D053264:B-Cell Activating Factor; D054804:Cathelicidins; C508598:IL4 protein, human; D007072:Immunoglobulin D; D007075:Immunoglobulin M; D007375:Interleukin-1; C505719:TNFSF13B protein, human; D015847:Interleukin-4; D003564:Cytidine Deaminase