Dependence of Immunoglobulin Class Switch Recombination in B Cells on Vesicular Release of ATP and CD73 Ectonucleotidase Activity

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)1824-1831
Number of pages8
JournalCell Reports
Volume3
Issue number6
DOIs
Publication statusPublished - Mar 27 2013

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Schena, F., Volpi, S., Faliti, C., Penco, F., Santi, S., Proietti, M., Schenk, U., Damonte, G., Salis, A., Bellotti, M., Fais, F., Tenca, C., Gattorno, M., Eibel, H., Rizzi, M., Warnatz, K., Idzko, M., Ayata, C. K., Rakhmanov, M., ... Traggiai, E. (2013). Dependence of Immunoglobulin Class Switch Recombination in B Cells on Vesicular Release of ATP and CD73 Ectonucleotidase Activity. Cell Reports, 3(6), 1824-1831. https://doi.org/10.1016/j.celrep.2013.05.022