title: Activation induced cytidine deaminase mutant (AID-His130Pro) from Hyper IgM 2 patient retained mutagenic activity on SHM artificial substrate.
abstract: Activation induced cytidine deaminase (AID) is an essential enzyme for class switch recombination (CSR) and somatic hypermutation (SHM) during secondary immune response. Mutations in the AICDA gene are responsible for Hyper IgM 2 syndrome where both CSR and SHM or only CSR are affected. Indeed, triggering either of the two mechanisms requires the DNA deamination activity of AID. Besides, different domains of AID may be differentially involved in CSR and SHM through their interaction with specific cofactors. Herein, we studied the AID-induced SHM activity of the AID-His130Pro mutant identified in a patient with Hyper IgM 2 syndrome. AID mutagenic activity was monitored by the reversion of nonsense mutations of the EGFP gene assessed by flow cytometry. We found that the His130Pro mutation, which affects CSR, preserves AID mutagenic activity. Indeed, the His130 residue is located in a putative specific CSR region in the APOBEC-like domain, known to involve CSR specific cofactors that probably play a major role in AID physiological activities.
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Tunisia; University Tunis El Manar, Tunis, Tunisia.
authors.forename: Hanen
authors.initials: H
authors.lastname: Ouadani
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Tunisia; University Tunis El Manar, Tunis, Tunisia.
authors.forename: Imen
authors.initials: I
authors.lastname: Ben-Mustapha
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Tunisia; University Tunis El Manar, Tunis, Tunisia.
authors.forename: Meriem
authors.initials: M
authors.lastname: Ben-Ali
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Tunisia.
authors.forename: Beya
authors.initials: B
authors.lastname: Larguèche
authors.affiliation: Biochemistry and Genetics Development Unit (URA CNRS 2581), Institut Pasteur Paris, France.
authors.forename: Tihana
authors.initials: T
authors.lastname: Jovanic
authors.affiliation: Laboratory of Lymphocyte Population Biology, Institut Pasteur Paris, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Garcia
authors.affiliation: Laboratory of Dynamics of the Genome, Institut Pasteur, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Arcangioli
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Tunisia.
authors.forename: Houda
authors.initials: H
authors.lastname: Elloumi-Zghal
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Tunisia.
authors.forename: Dahmani
authors.initials: D
authors.lastname: Fathallah
authors.affiliation: Department of Pediatrics, Hedi Chaker Hospital, Sfax, Tunisia.
authors.forename: Mongia
authors.initials: M
authors.lastname: Hachicha
authors.affiliation: Laboratory of Immunology, Habib Bourguiba Hospital, Sfax, Tunisia.
authors.forename: Hatem
authors.initials: H
authors.lastname: Masmoudi
authors.affiliation: Biochemistry and Genetics Development Unit (URA CNRS 2581), Institut Pasteur Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Rougeon
authors.affiliation: Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Tunisia; University Tunis El Manar, Tunis, Tunisia. Electronic address: ridha.barbouche@pasteur.rns.tn.
authors.forename: Mohamed-Ridha
authors.initials: MR
authors.lastname: Barbouche
mesh_terms: D015153:Blotting, Western; D003564:Cytidine Deaminase / Q000235:genetics*; D006801:Humans; D053306:Hyper-IgM Immunodeficiency Syndrome / Q000235:genetics*; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D019169:Jurkat Cells; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID mutagenic activity; Activation induced cytidine deaminase; Class switch recombination; Cofactors; Hyper IgM 2; Somatic hypermutation