Péron, S, Metin, A, Gardès, P et al. (5 more authors) (2008) Human PMS2 deficiency is associated with impaired immunoglobulin class switch recombination. Journal of Experimental Medicine, 205 (11). pp. 2465-2472. ISSN 0022-1007
Abstract
Immunoglobulin (Ig) class switch recombination (CSR) deficiencies are rare primary immunodeficiencies characterized by the lack of switched isotype (IgG/IgA/IgE) production. In some cases, CSR deficiencies can be associated with abnormal somatic hypermutation. Analysis of CSR deficiencies has helped reveal the key functions of CSR-triggering molecules, i.e., CD40L, CD40, and effector molecules such as activation-induced cytidine deaminase and uracil N-glycosylase. We report a new form of B cell–intrinsic CSR deficiency found in three patients with deleterious, homozygous mutations in the gene encoding the PMS2 component of the mismatch repair machinery. CSR was found partially defective in vivo and markedly impaired in vitro. It is characterized by the defective occurrence of double-strand DNA breaks (DSBs) in switch regions and abnormal formation of switch junctions. This observation strongly suggests a role for PMS2 in CSR-induced DSB generation.
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Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © Péron et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the fi rst 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/). |
Keywords: | HUMAN MISMATCH REPAIR; SOMATIC HYPERMUTATION; MUTL-ALPHA; MICE DEFICIENT; CUTTING EDGE; DNA BREAKS; HYPER-IGM; MLH1; MUTATIONS; MECHANISM |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) > Genetics (LIBACS) (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 01 Nov 2019 10:02 |
Last Modified: | 01 Nov 2019 10:02 |
Status: | Published |
Publisher: | Rockefeller University Press |
Identification Number: | 10.1084/jem.20080789 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98109 |
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