摘要
Mature B-cells express membrane IgM and IgD(of same specificity)through alternative splicing of a pre-mRNA encompassing constant(C)μand Cδgenes.After 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 functions.DNA-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 controversial.UNG is a key enzyme of base excision repair,which carries out faithful repair.Some 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.
基金
This work wassupported by ANR (projet EpiSwitch-3'RR 2016)
N.G. was supported by a grant fromthe Association de Specialisation et d'Orientation Scientifique (Lebanon) and themunicipality of Khiam (Lebanon)
H.l. is supported by CORC(FJA/NP 2015-109) and the University of Limoges. The authors are "Equipe Labellisée LIGUE 2018." We thank the GenoLim platform and the Cytometry platform of the University of Limoges forsequencing and cell sorting. F.B. is supported by Fondation Partenariale del'Universite de Limoges and ALURAD.