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Inherited Defects of Immunoglobulin Class Switch Recombination

  • Chapter
Diseases of DNA Repair

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 685))

Abstract

The investigation of an inherited primary immunodeficiency, the immunoglobulin class switch recombination deficiency, has allowed the delineation of complex molecular events that underlie antibody maturation in humans. The Activation-induced cytidine deaminase (AID)-deficiency, characterized by a defect in Class Switch Recombination (CSR) and somatic hypermutation, has revealed the master role of this molecule in the induction of DNA damage, the first step required for these two processes. The description that mutations in the gene encoding the Uracil-DNA glycosylase (UNG) lead to defective CSR has been essential for defining the DNA-editing activity of AID. Analysis of post meiotic segregation 2 (PMS2)-deficient patients gave evidence for the role of this mismatch repair enzyme in the generation of the DNA breaks that are required for CSR. Novel findings are awaited from the study of yet-genetically undefined CSR-deficiencies, probably leading to the identification of AID cofactor(s) and/or proteins involved in CSR-induced DNA

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Authors and Affiliations

  1. INSERM, U768, Université Paris Descartes, Faculté de Médecine René Descartes, Paris, F-75005, France

    Sven Kracker, Pauline Gardës & Anne Durandy

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  1. Sven Kracker
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  2. Pauline Gardës
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  3. Anne Durandy
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Correspondence to Anne Durandy .

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  1. School of Science and Technology, Nottingham Trent University, Nottingham, UK

    Shamim I. Ahmad BSc, MSc, PhD

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Kracker, S., Gardës, P., Durandy, A. (2010). Inherited Defects of Immunoglobulin Class Switch Recombination. In: Ahmad, S.I. (eds) Diseases of DNA Repair. Advances in Experimental Medicine and Biology, vol 685. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-6448-9_15

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