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.
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Acknowledgements
We thank A. Kirshenbaum and D. Metcalfe (US National Institutes of Health) for the mast cell line LAD2; F. Facchetti (Università di Brescia) for tissue samples; and R. Silver, R. Schreiner and F. Diaz (Weill Medical College of Cornell University) for primary lung mast cells and discussion of transcytosis assays. Supported by the US National Institutes of Health (R01 AI057653, R01 AI057653 supplement and R01 AI074378 to A.C.; and funds from T32 AI07621 to W.X.), the Cancer Research Institute (P.A.S.), The Irma T. Hirschl Charitable Trust (A.C.), the Ministerio de Ciencia e Innovación (Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica SAF 2008-02725 to A.C.) and Fondazione C. Golgi and Centro Immunodeficienze Mario Di Martino (A.P.).
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K.C. designed and did research and wrote the paper; W.X., M.W., B. He, E.B., E.-S.E., N.W.M. and P.R. did research and discussed data; P.A.S. discussed data; B.Hu. provided reagents and did research; A.Ch., A.M., M.C., J.L., K.R., C.C.-R., J.B.B. and A.P. provided blood and tissue samples and discussed data; and A.Ce. designed research, discussed data and wrote the paper.
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Chen, K., Xu, W., Wilson, M. et al. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell–stimulating programs in basophils. Nat Immunol 10, 889–898 (2009). https://doi.org/10.1038/ni.1748
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DOI: https://doi.org/10.1038/ni.1748
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