Dependence of immunoglobulin class switch recombination in B Cells on vesicular release of ATP and CD73 ectonucleotidase activity

Volpi, Stefano; Faliti, Caterina Elisa; Penco, Federica; Santi, Spartaco; Proietti, Michele; Schenk, Ursula; Damonte, Gianluca; Salis, Annalisa; Bellotti, Marta; Fais, Franco; Tenca, Claudya; Gattorno, Marco; Eibel, Hermann; Rizzi, Marta; Warnatz, Klaus; Idzko, Marco; Ayata, Cemil Korcan; Rakhmanov, Mirzokhid; Galli, Thierry; Martini, Alberto; Canossa, Marco; Grassi, Fabio; Traggiai, Elisabetta; Schena, Francesca

doi:10.1016/j.celrep.2013.05.022

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Journal article

Dependence of immunoglobulin class switch recombination in B Cells on vesicular release of ATP and CD73 ectonucleotidase activity

Volpi, Stefano Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
Faliti, Caterina Elisa Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Penco, Federica Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
Santi, Spartaco Department of Neuroscience and Brain Technologies, Fondazione Istituto Italiano di Tecnologia, Genova, Italy
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
Schenk, Ursula Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
Damonte, Gianluca Center of Excellence for Biomedical Research (CEBR)
Salis, Annalisa Center of Excellence for Biomedical Research (CEBR) - Department of Hearth Environmental and Life Science (DISTAV), University of Genova, Genova, Italy
Bellotti, Marta Center of Excellence for Biomedical Research (CEBR)
Fais, Franco Human Anatomy Section, Department of Experimental Medicine
Tenca, Claudya Human Anatomy Section, Department of Experimental Medicine
Gattorno, Marco Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
Eibel, Hermann Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
Rizzi, Marta Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
Warnatz, Klaus Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
Idzko, Marco Membrane Traffic in Neuronal and Epithelial Morphogenesis, INSERM ERL U950, Paris, France
Ayata, Cemil Korcan Membrane Traffic in Neuronal and Epithelial Morphogenesis, INSERM ERL U950, Paris, France
Rakhmanov, Mirzokhid Centre for Chronic Immunodeficiency, University Medical Centre Freiburg, Freiburg, Germany
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
Martini, Alberto Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
Canossa, Marco Department of Neuroscience and Brain Technologies, Fondazione Istituto Italiano di Tecnologia, Genova, Italy - European Brain Research Institute (EBRI), Rome, Italy
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
Traggiai, Elisabetta Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy
Schena, Francesca Department of Pediatrics, University of Genova and Pediatria II, Institute G Gaslini, Genova, Italy

27.06.2013

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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