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Research Article

Immunoglobulin Class Switch Recombination Is Initiated by Rare Cytosine Deamination Events at Switch Regions

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Article: e00125-20 | Received 26 Mar 2020, Accepted 01 Jun 2020, Published online: 03 Mar 2023

REFERENCES

  • Chaudhuri J, Alt FW. 2004. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat Rev Immunol 4:541–552. https://doi.org/10.1038/nri1395.
  • Stavnezer J, Guikema JE, Schrader CE. 2008. Mechanism and regulation of class switch recombination. Annu Rev Immunol 26:261–292. https://doi.org/10.1146/annurev.immunol.26.021607.090248.
  • Yu K, Lieber MR. 2019. Current insights into the mechanism of mammalian immunoglobulin class switch recombination. Crit Rev Biochem Mol Biol 54:333–351. https://doi.org/10.1080/10409238.2019.1659227.
  • Yu K, Lieber MR. 2003. Nucleic acid structures and enzymes in the immunoglobulin class switch recombination mechanism. DNA Repair (Amst) 2:1163–1174. https://doi.org/10.1016/j.dnarep.2003.08.010.
  • Bransteitter R, Pham P, Scharff MD, Goodman MF. 2003. Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci U S A 100:4102–4107. https://doi.org/10.1073/pnas.0730835100.
  • Chaudhuri J, Tian M, Khuong C, Chua K, Pinaud E, Alt FW. 2003. Transcription-targeted DNA deamination by the AID antibody diversification enzyme. Nature 422:726–730. https://doi.org/10.1038/nature01574.
  • Dickerson SK, Market E, Besmer E, Papavasiliou FN. 2003. AID mediates hypermutation by deaminating single stranded DNA. J Exp Med 197:1291–1296. https://doi.org/10.1084/jem.20030481.
  • Sohail A, Klapacz J, Samaranayake M, Ullah A, Bhagwat AS. 2003. Human activation-induced cytidine deaminase causes transcription-dependent, strand-biased C to U deaminations. Nucleic Acids Res 31:2990–2994. https://doi.org/10.1093/nar/gkg464.
  • Yu K, Huang FT, Lieber MR. 2004. DNA substrate length and surrounding sequence affect the activation-induced deaminase activity at cytidine. J Biol Chem 279:6496–6500. https://doi.org/10.1074/jbc.M311616200.
  • Ramiro AR, Stavropoulos P, Jankovic M, Nussenzweig MC. 2003. Transcription enhances AID-mediated cytidine deamination by exposing single-stranded DNA on the nontemplate strand. Nat Immunol 4:452–456. https://doi.org/10.1038/ni920.
  • Yu K, Chedin F, Hsieh CL, Wilson TE, Lieber MR. 2003. R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nat Immunol 4:442–451. https://doi.org/10.1038/ni919.
  • Zheng S, Vuong BQ, Vaidyanathan B, Lin JY, Huang FT, Chaudhuri J. 2015. Non-coding RNA generated following lariat debranching mediates targeting of AID to DNA. Cell 161:762–773. https://doi.org/10.1016/j.cell.2015.03.020.
  • Faili A, Aoufouchi S, Gueranger Q, Zober C, Leon A, Bertocci B, Weill JC, Reynaud CA. 2002. AID-dependent somatic hypermutation occurs as a DNA single-strand event in the BL2 cell line. Nat Immunol 3:815–821. https://doi.org/10.1038/ni826.
  • Rada C, Di Noia JM, Neuberger MS. 2004. Mismatch recognition and uracil excision provide complementary paths to both Ig switching and the A/T-focused phase of somatic mutation. Mol Cell 16:163–171. https://doi.org/10.1016/j.molcel.2004.10.011.
  • Chen Z, Viboolsittiseri SS, O’Connor BP, Wang JH. 2012. Target DNA sequence directly regulates the frequency of activation-induced deaminase-dependent mutations. J Immunol 189:3970–3982. https://doi.org/10.4049/jimmunol.1200416.
  • Shinkura R, Tian M, Smith M, Chua K, Fujiwara Y, Alt FW. 2003. The influence of transcriptional orientation on endogenous switch region function. Nat Immunol 4:435–441. https://doi.org/10.1038/ni918.
  • Nakamura M, Kondo S, Sugai M, Nazarea M, Imamura S, Honjo T. 1996. High frequency class switching of an IgM+ B lymphoma clone CH12F3 to IgA+ cells. Int Immunol 8:193–201. https://doi.org/10.1093/intimm/8.2.193.
  • Kim A, Han L, Santiago GE, Verdun RE, Yu K. 2016. Class-switch recombination in the absence of the IgH 3′ regulatory region. J Immunol 197:2930–2935. https://doi.org/10.4049/jimmunol.1600530.
  • Han L, Masani S, Yu K. 2011. Overlapping activation-induced cytidine deaminase hotspot motifs in Ig class-switch recombination. Proc Natl Acad Sci U S A 108:11584–11589. https://doi.org/10.1073/pnas.1018726108.
  • Ehrenstein MR, Neuberger MS. 1999. Deficiency in Msh2 affects the efficiency and local sequence specificity of immunoglobulin class-switch recombination: parallels with somatic hypermutation. EMBO J 18:3484–3490. https://doi.org/10.1093/emboj/18.12.3484.
  • Schrader CE, Edelmann W, Kucherlapati R, Stavnezer J. 1999. Reduced isotype switching in splenic B cells from mice deficient in mismatch repair enzymes. J Exp Med 190:323–330. https://doi.org/10.1084/jem.190.3.323.
  • Han L, Yu K. 2008. Altered kinetics of NHEJ and CSR in DNA ligase IV-deficient B cells. J Exp Med 205:2745–2753. https://doi.org/10.1084/jem.20081623.
  • Lebecque SG, Gearhart PJ. 1990. Boundaries of somatic mutation in rearranged immunoglobulin genes: 5′ boundary is near the promoter, and 3′ boundary is approximately 1 kb from V(D)J gene. J Exp Med 172:1717–1727. https://doi.org/10.1084/jem.172.6.1717.
  • Rada C, Milstein C. 2001. The intrinsic hypermutability of antibody heavy and light chain genes decays exponentially. EMBO J 20:4570–4576. https://doi.org/10.1093/emboj/20.16.4570.
  • Barreto V, Reina-San-Martin B, Ramiro AR, McBride KM, Nussenzweig MC. 2003. C-terminal deletion of AID uncouples class switch recombination from somatic hypermutation and gene conversion. Mol Cell 12:501–508. https://doi.org/10.1016/S1097-2765(03)00309-5.
  • Matthews AJ, Husain S, Chaudhuri J. 2014. Binding of AID to DNA does not correlate with mutator activity. J Immunol 193:252–257. https://doi.org/10.4049/jimmunol.1400433.
  • Nagaoka H, Muramatsu M, Yamamura N, Kinoshita K, Honjo T. 2002. Activation-induced deaminase (AID)-directed hypermutation in the immunoglobulin Smu region: implication of AID involvement in a common step of class switch recombination and somatic hypermutation. J Exp Med 195:529–534. https://doi.org/10.1084/jem.20012144.
  • Cortizas EM, Zahn A, Hajjar ME, Patenaude AM, Di Noia JM, Verdun RE. 2013. Alternative end-joining and classical nonhomologous end-joining pathways repair different types of double-strand breaks during class-switch recombination. J Immunol 191:5751–5763. https://doi.org/10.4049/jimmunol.1301300.
  • Kinoshita K, Harigai M, Fagarasan S, Muramatsu M, Honjo T. 2001. A hallmark of active class switch recombination: transcripts directed by I promoters on looped-out circular DNAs. Proc Natl Acad Sci U S A 98:12620–12623. https://doi.org/10.1073/pnas.221454398.
  • Pham P, Malik S, Mak C, Calabrese PC, Roeder RG, Goodman MF. 2019. AID-RNA polymerase II transcription-dependent deamination of IgV DNA. Nucleic Acids Res 47:10815–10829. https://doi.org/10.1093/nar/gkz821.
  • Pham P, Bransteitter R, Petruska J, Goodman MF. 2003. Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424:103–107. https://doi.org/10.1038/nature01760.
  • Schrader CE, Bradley SP, Vardo J, Mochegova SN, Flanagan E, Stavnezer J. 2003. Mutations occur in the Ig Smu region but rarely in Sgamma regions prior to class switch recombination. EMBO J 22:5893–5903. https://doi.org/10.1093/emboj/cdg550.
  • Basu U, Meng FL, Keim C, Grinstein V, Pefanis E, Eccleston J, Zhang T, Myers D, Wasserman CR, Wesemann DR, Januszyk K, Gregory RI, Deng H, Lima CD, Alt FW. 2011. The RNA exosome targets the AID cytidine deaminase to both strands of transcribed duplex DNA substrates. Cell 144:353–363. https://doi.org/10.1016/j.cell.2011.01.001.
  • Pefanis E, Wang J, Rothschild G, Lim J, Chao J, Rabadan R, Economides AN, Basu U. 2014. Noncoding RNA transcription targets AID to divergently transcribed loci in B cells. Nature 514:389–393. https://doi.org/10.1038/nature13580.
  • Pefanis E, Wang J, Rothschild G, Lim J, Kazadi D, Sun J, Federation A, Chao J, Elliott O, Liu ZP, Economides AN, Bradner JE, Rabadan R, Basu U. 2015. RNA exosome-regulated long non-coding RNA transcription controls super-enhancer activity. Cell 161:774–789. https://doi.org/10.1016/j.cell.2015.04.034.
  • Cerritelli SM, Crouch RJ. 2009. Ribonuclease H: the enzymes in eukaryotes. FEBS J 276:1494–1505. https://doi.org/10.1111/j.1742-4658.2009.06908.x.
  • Qiao Q, Wang L, Meng FL, Hwang JK, Alt FW, Wu H. 2017. AID recognizes structured DNA for class switch recombination. Mol Cell 67:361–373.e4. https://doi.org/10.1016/j.molcel.2017.06.034.
  • Min IM, Schrader CE, Vardo J, Luby TM, D’Avirro N, Stavnezer J, Selsing E. 2003. The Smu tandem repeat region is critical for Ig isotype switching in the absence of Msh2. Immunity 19:515–524. https://doi.org/10.1016/S1074-7613(03)00262-0.
  • Min IM, Rothlein LR, Schrader CE, Stavnezer J, Selsing E. 2005. Shifts in targeting of class switch recombination sites in mice that lack mu switch region tandem repeats or Msh2. J Exp Med 201:1885–1890. https://doi.org/10.1084/jem.20042491.
  • Ling AK, So CC, Le MX, Chen AY, Hung L, Martin A. 2018. Double-stranded DNA break polarity skews repair pathway choice during intrachromosomal and interchromosomal recombination. Proc Natl Acad Sci U S A 115:2800–2805. https://doi.org/10.1073/pnas.1720962115.
  • Ran FA, Hsu PD, Wright J, Agarwala V, Scott DA, Zhang F. 2013. Genome engineering using the CRISPR-Cas9 system. Nat Protoc 8:2281–2308. https://doi.org/10.1038/nprot.2013.143.

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