Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils.
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.
Chen
Kang
K
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York, USA.
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
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
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