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

Full 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.

Author information

Author/s: Chen, Kang (K); Xu, Weifeng (W); Wilson, Melanie (M); He, Bing (B); Miller, Norman W (NW); Bengtén, Eva (E); Edholm, Eva-Stina (ES); Santini, Paul A (PA); Rath, Poonam (P); Chiu, April (A); Cattalini, Marco (M); Litzman, Jiri (J); B Bussel, James (J); Huang, Bihui (B); Meini, Antonella (A); Riesbeck, Kristian (K); Cunningham-Rundles, Charlotte (C); Plebani, Alessandro (A); Cerutti, Andrea (A);

Affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA.

Grants: R01 AI057653 (Agency:NIAID NIH HHS) ; R01 AI074378 (Agency:NIAID NIH HHS) ; T32 AI07621 (Agency:NIAID NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Nature immunology (Nat Immunol), published in United States. (Language: eng)

Reference: 2009-Aug; vol 10 (issue 8) : pp 889-98

Dates: Created 2009/07/21; Completed 2009/10/14;

PMID: 19561614, status: MEDLINE (last retrieval date: 10/14/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

B-Cell Activating Factor - metabolism
B-Lymphocytes - immunology
Basophils - immunology; metabolism
Cathelicidins - metabolism
Cell Line
Cytidine Deaminase - metabolism
Familial Mediterranean Fever - immunology
Haemophilus influenzae - growth & development; physiology
Humans

Immunoglobulin Class Switching
Immunoglobulin D - biosynthesis; immunology
Immunoglobulin M - immunology
Interleukin-1 - metabolism
Interleukin-4 - metabolism
Mevalonate Kinase Deficiency - immunology
Moraxella (Branhamella) catarrhalis - growth & development; physiology
Protein Binding
Respiratory Mucosa - immunology; metabolism; microbiology

Associated Chemicals: B-Cell Activating Factor (0) ; Cathelicidins (0) ; IL4 protein, human (0) ; Immunoglobulin D (0) ; Immunoglobulin M (0) ; Interleukin-1 (0) ; TNFSF13B protein, human (0) ; Interleukin-4 (207137-56-2) ; Cytidine Deaminase (EC 3.5.4.5)

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