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¹ Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital Huddinge, SE-14186, Stockholm, Sweden
² Department of Immunology, Erasmus Medical Center, 3000 CA, Rotterdam, Netherlands
³ Department of Pediatric Immunology, Newcastle General Hospital, Newcastle NE4 6BE, England, UK

CORRESPONDENCE Qiang Pan-Hammarström: Qiang.Pan-Hammarstrom{at}ki.se

DNA double-strand breaks (DSBs) introduced in the switch (S) regions are intermediates during immunoglobulin class switch recombination (CSR). These breaks are subsequently recognized, processed, and joined, leading to recombination of the two S regions. Nonhomologous end-joining (NHEJ) is believed to be the principle mechanism involved in DSB repair during CSR. One important component in NHEJ, Artemis, has however been considered to be dispensable for efficient CSR. In this study, we have characterized the S recombinational junctions from Artemis-deficient human B cells. Sµ–S junctions could be amplified from all patients tested and were characterized by a complete lack of "direct" end-joining and a remarkable shift in the use of an alternative, microhomology-based end-joining pathway. Sµ–S junctions could only be amplified from one patient who carries "hypomorphic" mutations. Although these Sµ–S junctions appear to be normal, a significant increase of an unusual type of sequential switching from immunoglobulin (Ig)M, through one IgG subclass, to a different IgG subclass was observed, and the S–S junctions showed long microhomologies. Thus, when the function of Artemis is impaired, varying modes of CSR junction resolution may be used for different S regions. Our findings strongly link Artemis to the predominant NHEJ pathway during CSR.

© 2008 Du et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

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This article has been cited by other articles:

• Rivera-Munoz, P., Soulas-Sprauel, P., Le Guyader, G., Abramowski, V., Bruneau, S., Fischer, A., Paques, F., de Villartay, J.-P. (2009). Reduced immunoglobulin class switch recombination in the absence of Artemis. Blood 114: 3601-3609 [Abstract] [Full Text]  

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