Class switch recombination junctions are not affected by the absence of the immunoglobulin heavy chain Eμenhancer

摘要

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 regions.CSR 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 region.During 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.However,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.