Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination

Kohsuke Imai; Geir Slupphaug; Wen I. Lee; Patrick Revy; Shigeaki Nonoyama; Nadia Catalan; Leman Yel; Monique Forveille; Bodil Kavli; Hans E. Krokan; Hans D. Ochs; Alain Fischer; Anne Durandy

doi:10.1038/ni974

Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination

Kohsuke Imai, Geir Slupphaug, Wen I. Lee, Patrick Revy, Shigeaki Nonoyama, Nadia Catalan, Leman Yel, Monique Forveille, Bodil Kavli, Hans E. Krokan, Hans D. Ochs, Alain Fischer, Anne Durandy^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal Article › peer-review

579 Scopus citations

Abstract

Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice. We show here that recessive mutations of the gene encoding uracil-DNA glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome. Together with the finding that nuclear UNG expression was induced in activated B cells, these data support a model of CSR and SHM in which AID deaminates cytosine into uracil in targeted DNA (immunoglobulin switch or variable regions), followed by uracil removal by UNG.

Original language	English
Pages (from-to)	1023-1028
Number of pages	6
Journal	Nature Immunology
Volume	4
Issue number	10
DOIs	https://doi.org/10.1038/ni974
State	Published - 01 10 2003
Externally published	Yes

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title = "Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination",

abstract = "Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice. We show here that recessive mutations of the gene encoding uracil-DNA glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome. Together with the finding that nuclear UNG expression was induced in activated B cells, these data support a model of CSR and SHM in which AID deaminates cytosine into uracil in targeted DNA (immunoglobulin switch or variable regions), followed by uracil removal by UNG.",

author = "Kohsuke Imai and Geir Slupphaug and Lee, \{Wen I.\} and Patrick Revy and Shigeaki Nonoyama and Nadia Catalan and Leman Yel and Monique Forveille and Bodil Kavli and Krokan, \{Hans E.\} and Ochs, \{Hans D.\} and Alain Fischer and Anne Durandy",

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T1 - Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination

AU - Imai, Kohsuke

AU - Slupphaug, Geir

AU - Lee, Wen I.

AU - Revy, Patrick

AU - Nonoyama, Shigeaki

AU - Catalan, Nadia

AU - Yel, Leman

AU - Forveille, Monique

AU - Kavli, Bodil

AU - Krokan, Hans E.

AU - Ochs, Hans D.

AU - Fischer, Alain

AU - Durandy, Anne

PY - 2003/10/1

Y1 - 2003/10/1

N2 - Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice. We show here that recessive mutations of the gene encoding uracil-DNA glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome. Together with the finding that nuclear UNG expression was induced in activated B cells, these data support a model of CSR and SHM in which AID deaminates cytosine into uracil in targeted DNA (immunoglobulin switch or variable regions), followed by uracil removal by UNG.

AB - Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice. We show here that recessive mutations of the gene encoding uracil-DNA glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome. Together with the finding that nuclear UNG expression was induced in activated B cells, these data support a model of CSR and SHM in which AID deaminates cytosine into uracil in targeted DNA (immunoglobulin switch or variable regions), followed by uracil removal by UNG.

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SP - 1023

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JO - Nature Immunology

JF - Nature Immunology

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ER -

Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination

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