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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
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    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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  • English
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Medicine
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https://n2t.net/ark:/12658/srd1318923
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