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Cellular & Molecular Immunology 2019年第7期16卷 671-673页

作者： Hussein Issaoui nour ghazzaui Mélissa Ferrad François Boyer Yves Denizot UMR CNRS 7276 INSERM U1262Equipe Labellisée LIGUE 2018University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance

After encountering antigen,B-cells undergo class switch recombination(CSR)that substitutes the constant(C)μgene with Cγ,Cε,or Cα,thereby generating IgG,IgE,and IgA antibodies with new effector functions but the same antigenic specificity.1 The DNA-editing enzyme activation-induced deaminase(AID)is required for CSR by targeting specific DNA switch(S)regions preceding the C region,except Cδ.2 Sμis the donor region,while Sγ,ε,αare the acceptor *** is controlled in cis by the immunoglobulin heavy chain(IgH)3’regulatory region(3’RR).3 The 3’RR is essential to poise AID on the S acceptor *** CSR IgH,intrachromosomal interactions(schematized in Fig.1a)are found between the 3’RR and the intronic Eμenhancer.1,4 Looping allows transcriptional binding activators to enhancers to facilitate ***,CSR is only modestly influenced by Eμdeletion.5–7 During CSR,two different DNA repair pathways take place:the classical nonhomologous end joining(c-NHEJ)and the alternative end joining(A-EJ)pathways.

关键词： joining thereby generating

High-throughput sequencing reveals similar molecular signatures for class switch recombination junctions for theγandαisotypes

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Cellular & Molecular Immunology 2019年第1期16卷 90-92页

作者： ussein Issaoui nour ghazzaui Alexis Saintamand Yves Denizot François Boyer UMR CNRS 7276 INSERM U1262CBRSLimoges Universityrue Pr.DescottesLimoges 87025France INSERM U1236 Rennes 1 UniversityRennesFrance

INTRODUCTION After encountering an antigen,B cells undergo class switch recombination(CSR),which substitutes the Cμgene with Cγ,Cε,or Cαto generate IgG,IgE,and IgA antibodies with the same antigenic specificity but new effector functions.1 The DNAediting enzyme activation-induced deaminase(AID)is essential for CSR by targeting switch(S)regions preceding Cμ(namely,the Sμdonor region)and the Cγ,Cε,and Cαgenes(namely,the Sγ,ε,αacceptor regions).1 Cis-and trans-controlled DNA double strand beaks are generated during this process.2–6 Recruitment of DNA repair factors that facilitate the end-joining process is a crucial step of class switch *** pathways are implicated in this end *** classical non-homogenous end joining(c-NHEJ)pathway ligates DNA ends with no or little *** contrast,the alternative end joining(A-EJ)pathways is used to ligate DNA ends that have microhomology.

关键词： functions. process. joining

Deletion of the immunoglobulin heavy chain 3′ regulatory region super-enhancer affects somatic hypermutation in B1 B cells

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Cellular & Molecular Immunology 2019年第2期16卷 195-197页

作者： Issaoui Hussein ghazzaui nour Boyer François Denizot Yves Saintamand Alexis Centre National de la Recherche Scientifique UnitéMixte de Recherche 7276 Institut National de la Santéet de la Recherche Médicale U1262CBRSrue du Pr.Descottes87025 LimogesFrance INSERM U1236 UniversitéRennes 1RennesFrance

Mouse B1 B cells originate in the embryonic liver and are the major B-cell population in the peritoneal and pleural cavities.1–5 By contrast,mouse B2 B cells originate in the bone marrow and are the major B-cell population in the bone marrow,spleen,and blood.B1 and B2 B cells differ not only in their origin and locations,but also in their antigen specificity,cell surface markers,capacities for class-switch recombination(CSR)and somatic hypermutation(SHM).IgH cis-regulatory regions and,particularly,transcriptional super-enhancers are major locus regulators under both normal and pathological conditions.6,7 Important differences have been found regarding the ability of the IgH 3′regulatory region(3′RR)super-enhancer to control the B1 and B2 B-cell fate.

关键词： spleen specificity peritoneal

IgD class switch recombination is not controlled through the immunoglobulin heavy chain 3′ regulatory region super-enhancer

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Cellular & Molecular Immunology 2017年第10期14卷 871-874页

作者： Hussein Issaoui nour ghazzaui Alexis Saintamand Yves Denizot François Boyer UMR CNRS 7276 University of LimogesCBRS87025 LimogesFrance Present address:INSERM U1236 UniversitéRennes 1RennesFrance

In secondary lymphoid organs,mature B cells express membrane immunoglobulin(Ig)of M and D isotypes(IgM and IgD,respectively)of the same specificity through alternative splicing of a pre-mRNA encompassing the VDJ variable region and Cμand Cδheavy chain constant exons.1 After encountering antigen,B cells undergo class switch recombination(CSR)by which the Cμgene is substituted with Cγ,Cεor Cα,thereby generating IgG,IgE and IgA antibodies of the same antigenic specificity but with new effector *** requires the DNA-editing enzyme activation-induced deaminase(AID).

关键词： functions. substituted thereby

Uracil-DNA glycosylase is not implicated in the choice of the DNA repair pathway during B-cell class switch recombination

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Cellular & Molecular Immunology 2019年第1期16卷 93-95页

作者： nour ghazzaui Hussein Issaoui Alexis Saintamand Yves Denizot François Boyer UMR CNRS 7276 INSERM U1262University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance INSERM U1236 Rennes 1 UniversityRennesFrance

Mature B-cells express membrane IgM and IgD(of same specificity)through alternative splicing of a pre-mRNA encompassing constant(C)μand Cδ*** encountering antigen,Bcells undergo class switch recombination(CSR)that substitutes the Cμgene with Cγ,Cε,or Cα,thereby generating IgG,IgE,and IgA antibodies with the same antigenic specificity but new effector ***-editing enzyme activation-induced deaminase(AID)is essential for CSR by targeting switch(S)regions preceding Cμ(namely,the Sμdonor region)and the Cγ,Cε,and Cαgenes(namely,the Sγ,ε,αacceptor regions).1,2 CSR is controlled in cis by IgH locus super-enhancers3 and in trans by a wide spectrum of enzymes and proteins.1,2 Among them,the role of the uracil DNA glycosylase(UNG)remains *** is a key enzyme of base excision repair,which carries out faithful *** authors estimate that during CSR,the UNG enzymatic activity removes the AID-induced dC to dU converted base of singlestrand DNA,generating abasic sites and leading to DNA strand breaks.1 For other authors,the role of UNG is to stabilize the S–S synapse and to recruit DNA repair factors that facilitate the endjoining process.4,5 Thus,the classical non-homogenous end joining pathway would be increased over the alternative end joining(A-EJ)pathway in UNG-deficient mice,4 suggesting an intriguing role of UNG in promoting the A-EJ pathway.

关键词： generating joining specificity

The IgH 3′ regulatory region super-enhancer does not control IgA class switch recombination in the B1 lineage

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Cellular & Molecular Immunology 2018年第3期15卷 289-291页

作者： Hussein Issaoui nour ghazzaui Alexis Saintamand Claire Carrion Christelle Oblet Yves Denizot CNRS UMR 7276 CRIBLUniversitéde LimogesLimogesFrance INSERM U1236 UniversitéRennes 1RennesFrance

The bone marrow-derived B2 population represents the vast majority of bone marrow,blood,lymph node and splenic *** B1 B-cells mostly originate during embryonic life in the liver and represent the main B-cell population in the pleural and peritoneal cavities.1,2,3,4,5 B1 and B2 B-cells differ in their origin,antigen specificity,cell surface markers,tissue distribution and capacity for class switch recombination(CSR).Schematically,B1 B-cells appear earlier than B2 B-cells during fetal development and maintain their self-renewal ability throughout their life.

关键词： maintain specificity mostly

Molecular analysis of γ1, γ3, and α class switch recombination junctions in APOBEC3-deficient mice using high-throughput sequencing

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Cellular & Molecular Immunology 2020年第4期17卷 418-420页

作者： Hussein Issaoui Mélissa Ferrad nour ghazzaui Sandrine Lecardeur Jeanne Cook-Moreau François Boyer Yves Denizot UMR CNRS 7276 INSERM U1262Equipe Labellisée LIGUE 2018University of LimogesCBRSrue Pr.Descottes87025 LimogesFrance

Activation-induced deaminase(AID)is required for immunoglobulin(Ig)class switch recombination(CSR),in which the constant(C)μgene of IgM is substituted with C_(γ),C_(ε),or C_(α),thereby generating IgG,IgE,and IgA antibodies,respectively,with new effector functions but the same antigenic specificity.1 AID targets specific DNA switch(S)regions preceding C regions except for Cδ.2 Sμis usually the donor region,while Sγ,ε,αare the acceptor *** deaminates C into U on single-stranded DNA by targeting the WRCY(W=A/T,R=A/G,and Y=C/T)hot motif and,to a lesser extent,the SYC(S=G/C,Y=C/T)cold motif.3,4 AID is a member of the apolipoprotein B editing complex(APOBEC)*** APOBEC genes,a family of evolutionarily conserved cytidine deaminases,APOBEC3 is implicated in diverse cell functions including innate immunity against retroviruses.4 The DNA-editing APOBEC3 enzymes have recently attracted attention due to their involvement in cancer and potential applications in gene editing.5–7 While a single copy of each APOBEC3 gene is present in rodents,seven copies of each APOBEC3 gene are found in humans.

关键词： immunity involvement thereby

Trans-silencing effect of the 3′RR immunoglobulin heavy chain enhancer on Igκtranscription at the pro-B cell stage

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Cellular & Molecular Immunology 2019年第7期16卷 668-670页

作者： nour ghazzaui Hussein Issaoui Ophélie Alyssa Martin Alexis Saintamand Jeanne Cook-Moreau Yves Denizot François Boyer CNRS UMR 7276 Inserm U1262Universitéde LimogesLimogesFrance Present address:Inserm U1236 UniversitéRennes 1RennesFrance

Due to their impact on nuclear organization,enhancers are master regulators of cell fate.1,2 The immunoglobulin heavy chain(IgH)locus undergoes numerous changes(such as transcription,accessibility,DNA breaks,and mutations)throughout B-cell *** of these events are controlled by the IgH 3′regulatory region(3′RR).The 3′RR is the master control element of mature B-cell IgH transcription,3 somatic hypermutation(SHM),4,5 conventional class switch recombination(CSR),4,6–10 and locus suicide recombination(LSR).11 In contrast,the 3′RR is expected to be dispensable for V(D)J recombination.12,13 During Bcell development,the heavy and light chain loci are poised for their VDJ and VJ rearrangements,*** IgH locus rearranges first,with D-J joining at the pro-B-cell stages,followed by V-DJ joining at the pre-B-cell *** Igk locus is poised for VJ rearrangements at the pre-B cell stage.

关键词： effect joining recombination

Retraction Note:3′RR and 5′Eμimmunoglobulin heavy chain enhancers are independent engines of locus remodeling

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Cellular & Molecular Immunology 2021年第8期18卷 2082-2082页

作者： nour ghazzaui Hussein Issaoui François Boyer Ophélie Alyssa Martin Alexis Saintamand Yves Denizot CNRS UMR 7276 Inserm U1262Universitéde LimogesLimogesFrance Present address:Inserm U1236 UniversitéRennes 1RennesFrance

The authors have retracted this *** the publication of this correspondence,it came to the authors’attention that the control RAG2^(−/−)mouse was a RAG2^(−/−)γc^(−/−)*** point resulted in the conclusions being consid... 详细信息

关键词： journal correspondence conclusions

Retraction Note:Trans-silencing effect of the 3′RR immunoglobulin heavy chain enhancer on Igκtranscription at the pro-B cell stage

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Cellular & Molecular Immunology 2021年第8期18卷 2081-2081页

作者： nour ghazzaui Hussein Issaoui Ophélie Alyssa Martin Alexis Saintamand Jeanne Cook-Moreau Yves Denizot François Boyer Present address:Inserm U1236 UniversitéRennes 1RennesFrance CNRS UMR 7276 Inserm U1262Universitéde LimogesLimogesFrance

关键词： journal correspondence Igκ