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Blood, 22 October 2009, Vol. 114, No. 17, pp. 3601-3609. Prepublished online as a Blood First Edition Paper on August 19, 2009; DOI 10.1182/blood-2008-11-188383. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2008-11-188383v1 114/17/3601    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Rivera-Munoz, P. Articles by de Villartay, J.-P. PubMed PubMed Citation Articles by Rivera-Munoz, P. Articles by de Villartay, J.-P. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Reduced immunoglobulin class switch recombination in the absence of Artemis Paola Rivera-Munoz1,2,*, Pauline Soulas-Sprauel1,2,*, Gwenaël Le Guyader1,2, Vincent Abramowski1,2, Sylvia Bruneau3, Alain Fischer1,2,4, Frédéric Pâques3, and Jean-Pierre de Villartay1,2,4 1 Inserm U768 and 2 Université Paris-Descartes, Faculté de Médecine René Descartes, Paris; 3 Cellectis SA, Romainville; and 4 Assistance Publique-Hopitaux de Paris, Hôpital Necker Enfants Malades, Service d'Immunologie et d'Hématologie Pédiatrique, Paris, France Nonhomologous end-joining DNA repair factors, including Artemis, are all required for the repair of DNA double-strand breaks, which occur during the assembly of the variable antigen recognition domain of B-cell receptors and T-cell receptors through the V(D)J recombination. Mature B cells further shape their immunoglobulin repertoire on antigen recognition notably through the class switch recombination (CSR) process. To analyze the role of Artemis during CSR, we developed a mature B-cell–specific Artemis conditional knockout mouse to bypass the absence of B cells caused by its early deficit. Although CSR is not overwhelmingly affected in these mice, class switching to certain isotypes is clearly reduced both in vitro on B-cell activation and in vivo after keyhole limpet hemocyanin immunization. The reduced CSR in Artemis-deficient B cells is accompanied by the increase in DNA microhomology usage at CSR junctions, the imprint of an alternative DNA end-joining pathway. Likewise, significant increase in DNA microhomology usage is the signature of CSR junctions obtained from human RS-SCID patients harboring hypomorphic Artemis mutations. Altogether, this indicates that Artemis participates in the repair of a subset of DNA breaks generated during CSR. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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