Dependence of immunoglobulin class switch recombination in B Cells on vesicular release of ATP and CD73 ectonucleotidase activity
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Volpi, Stefano
Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
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Faliti, Caterina Elisa
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Penco, Federica
Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
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Santi, Spartaco
Department of Neuroscience and Brain Technologies, Fondazione Istituto Italiano di Tecnologia, Genova, Italy
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Proietti, Michele
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Dipartimento di Biologia e Genetica per le Scienze Mediche, Università di Milano, Milan, Italy
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Schenk, Ursula
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
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Damonte, Gianluca
Center of Excellence for Biomedical Research (CEBR)
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Salis, Annalisa
Center of Excellence for Biomedical Research (CEBR) - Department of Hearth Environmental and Life Science (DISTAV), University of Genova, Genova, Italy
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Bellotti, Marta
Center of Excellence for Biomedical Research (CEBR)
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Fais, Franco
Human Anatomy Section, Department of Experimental Medicine
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Tenca, Claudya
Human Anatomy Section, Department of Experimental Medicine
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Gattorno, Marco
Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
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Eibel, Hermann
Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
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Rizzi, Marta
Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
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Warnatz, Klaus
Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
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Idzko, Marco
Membrane Traffic in Neuronal and Epithelial Morphogenesis, INSERM ERL U950, Paris, France
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Ayata, Cemil Korcan
Membrane Traffic in Neuronal and Epithelial Morphogenesis, INSERM ERL U950, Paris, France
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Rakhmanov, Mirzokhid
Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
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Galli, Thierry
Institut Jacques Monod, CNRS, UMR 7592, Université Paris Diderot, Sorbonne Paris Citè, Paris, France - Membrane Traffic in Neuronal and Epithelial Morphogenesis, INSERM ERL U950, Paris, France
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Martini, Alberto
Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
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Canossa, Marco
Department of Neuroscience and Brain Technologies, Fondazione Istituto Italiano di Tecnologia, Genova, Italy - European Brain Research Institute (EBRI), Rome, Italy
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Grassi, Fabio
Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland - Dipartimento di Biologia e Genetica per le Scienze Mediche, Università di Milano, Milan, Italy
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Traggiai, Elisabetta
Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
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Schena, Francesca
Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
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Published in:
- Cell report. - 2013, vol. 3, no. 6, p. 1824-1831
English
Immunoglobulin (Ig) isotype diversification by class switch recombination (CSR) is an essential process for mounting a protective humoral immune response. Ig CSR deficiencies in humans can result from an intrinsic B cell defect; however, most of these deficiencies are still molecularly undefined and diagnosed as common variable immunodeficiency (CVID). Here, we show that extracellular adenosine critically contributes to CSR in human naive and IgM memory B cells. In these cells, coordinate stimulation of B cell receptor and toll-like receptors results in the release of ATP stored in Ca2+-sensitive secretory vesicles. Plasma membrane ectonucleoside triphosphate diphosphohydrolase 1 CD39 and ecto-5′-nucleotidase CD73 hydrolyze ATP to adenosine, which induces CSR in B cells in an autonomous fashion. Notably, CVID patients with impaired class-switched antibody responses are selectively deficient in CD73 expression in B cells, suggesting that CD73-dependent adenosine generation contributes to the pathogenesis of this disease.
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https://n2t.net/ark:/12658/srd1318923
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