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Nucleic Acids Res. Feb 11, 1993; 21(3): 365–372.
PMCID: PMC309126

DNA sequences at immunoglobulin switch region recombination sites.


The immunoglobulin heavy chain switch from synthesis of IgM to IgG, IgA or IgE is mediated by a DNA recombination event. Recombination occurs within switch regions, 2-10 kb segments of DNA that lie upstream of heavy chain constant region genes. A compilation of DNA sequences at more than 150 recombination sites within heavy chain switch regions is presented. Switch recombination does not appear to occur by homologous recombination. An extensive search for a recognition motif failed to find such a sequence, implying that switch recombination is not a site-specific event. A model for switch recombination that involves illegitimate priming of one switch region on another, followed by error-prone DNA synthesis, is proposed.

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  • French DL, Laskov R, Scharff MD. The role of somatic hypermutation in the generation of antibody diversity. Science. 1989 Jun 9;244(4909):1152–1157. [PubMed]
  • Sakano H, Maki R, Kurosawa Y, Roeder W, Tonegawa S. Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes. Nature. 1980 Aug 14;286(5774):676–683. [PubMed]
  • Dunnick W, Rabbitts TH, Milstein C. An immunoglobulin deletion mutant with implications for the heavy-chain switch and RNA splicing. Nature. 1980 Aug 14;286(5774):669–675. [PubMed]
  • Davis MM, Kim SK, Hood LE. DNA sequences mediating class switching in alpha-immunoglobulins. Science. 1980 Sep 19;209(4463):1360–1365. [PubMed]
  • Kataoka T, Miyata T, Honjo T. Repetitive sequences in class-switch recombination regions of immunoglobulin heavy chain genes. Cell. 1981 Feb;23(2):357–368. [PubMed]
  • Stanton LW, Marcu KB. Nucleotide sequence and properties of the murine gamma 3 immunoglobulin heavy chain gene switch region: implications for successive C gamma gene switching. Nucleic Acids Res. 1982 Oct 11;10(19):5993–6006. [PMC free article] [PubMed]
  • Nikaido T, Yamawaki-Kataoka Y, Honjo T. Nucleotide sequences of switch regions of immunoglobulin C epsilon and C gamma genes and their comparison. J Biol Chem. 1982 Jul 10;257(13):7322–7329. [PubMed]
  • Mills FC, Brooker JS, Camerini-Otero RD. Sequences of human immunoglobulin switch regions: implications for recombination and transcription. Nucleic Acids Res. 1990 Dec 25;18(24):7305–7316. [PMC free article] [PubMed]
  • von Schwedler U, Jäck HM, Wabl M. Circular DNA is a product of the immunoglobulin class switch rearrangement. Nature. 1990 May 31;345(6274):452–456. [PubMed]
  • Iwasato T, Shimizu A, Honjo T, Yamagishi H. Circular DNA is excised by immunoglobulin class switch recombination. Cell. 1990 Jul 13;62(1):143–149. [PubMed]
  • Matsuoka M, Yoshida K, Maeda T, Usuda S, Sakano H. Switch circular DNA formed in cytokine-treated mouse splenocytes: evidence for intramolecular DNA deletion in immunoglobulin class switching. Cell. 1990 Jul 13;62(1):135–142. [PubMed]
  • Gritzmacher CA. Molecular aspects of heavy-chain class switching. Crit Rev Immunol. 1989;9(3):173–200. [PubMed]
  • Esser C, Radbruch A. Immunoglobulin class switching: molecular and cellular analysis. Annu Rev Immunol. 1990;8:717–735. [PubMed]
  • Yoshida K, Matsuoka M, Usuda S, Mori A, Ishizaka K, Sakano H. Immunoglobulin switch circular DNA in the mouse infected with Nippostrongylus brasiliensis: evidence for successive class switching from mu to epsilon via gamma 1. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7829–7833. [PMC free article] [PubMed]
  • Iwasato T, Arakawa H, Shimizu A, Honjo T, Yamagishi H. Biased distribution of recombination sites within S regions upon immunoglobulin class switch recombination induced by transforming growth factor beta and lipopolysaccharide. J Exp Med. 1992 Jun 1;175(6):1539–1546. [PMC free article] [PubMed]
  • DePinho R, Kruger K, Andrews N, Lutzker S, Baltimore D, Alt FW. Molecular basis of heavy-chain class switching and switch region deletion in an Abelson virus-transformed cell line. Mol Cell Biol. 1984 Dec;4(12):2905–2910. [PMC free article] [PubMed]
  • Petrini J, Dunnick WA. Products and implied mechanism of H chain switch recombination. J Immunol. 1989 Apr 15;142(8):2932–2935. [PubMed]
  • Jäck HM, McDowell M, Steinberg CM, Wabl M. Looping out and deletion mechanism for the immunoglobulin heavy-chain class switch. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1581–1585. [PMC free article] [PubMed]
  • Yancopoulos GD, DePinho RA, Zimmerman KA, Lutzker SG, Rosenberg N, Alt FW. Secondary genomic rearrangement events in pre-B cells: VHDJH replacement by a LINE-1 sequence and directed class switching. EMBO J. 1986 Dec 1;5(12):3259–3266. [PMC free article] [PubMed]
  • Dunnick W, Wilson M, Stavnezer J. Mutations, duplication, and deletion of recombined switch regions suggest a role for DNA replication in the immunoglobulin heavy-chain switch. Mol Cell Biol. 1989 May;9(5):1850–1856. [PMC free article] [PubMed]
  • Ott DE, Marcu KB. Molecular requirements for immunoglobulin heavy chain constant region gene switch-recombination revealed with switch-substrate retroviruses. Int Immunol. 1989;1(6):582–591. [PubMed]
  • Owens JD, Jr, Finkelman FD, Mountz JD, Mushinski JF. Nonhomologous recombination at sites within the mouse JH-C delta locus accompanies C mu deletion and switch to immunoglobulin D secretion. Mol Cell Biol. 1991 Nov;11(11):5660–5670. [PMC free article] [PubMed]
  • Szurek P, Petrini J, Dunnick W. Complete nucleotide sequence of the murine gamma 3 switch region and analysis of switch recombination sites in two gamma 3-expressing hybridomas. J Immunol. 1985 Jul;135(1):620–626. [PubMed]
  • Petrini J, Shell B, Hummel M, Dunnick W. The immunoglobulin heavy chain switch: structural features of gamma 1 recombinant switch regions. J Immunol. 1987 Mar 15;138(6):1940–1946. [PubMed]
  • Gerstein RM, Frankel WN, Hsieh CL, Durdik JM, Rath S, Coffin JM, Nisonoff A, Selsing E. Isotype switching of an immunoglobulin heavy chain transgene occurs by DNA recombination between different chromosomes. Cell. 1990 Nov 2;63(3):537–548. [PubMed]
  • Greenberg R, Lang RB, Diamond MS, Marcu KB. A switch region inversion contributes to the aberrant rearrangement of a mu immunoglobulin heavy chain gene in MPC-11 cells. Nucleic Acids Res. 1982 Dec 11;10(23):7751–7761. [PMC free article] [PubMed]
  • Neuberger MS, Calabi F. Reciprocal chromosome translocation between c-myc and immunoglobulin gamma 2b genes. Nature. 1983 Sep 15;305(5931):240–243. [PubMed]
  • Lang RB, Stanton LW, Marcu KB. On immunoglobulin heavy chain gene switching: two gamma 2b genes are rearranged via switch sequences in MPC-11 cells but only one is expressed. Nucleic Acids Res. 1982 Jan 22;10(2):611–630. [PMC free article] [PubMed]
  • Obata M, Kataoka T, Nakai S, Yamagishi H, Takahashi N, Yamawaki-Kataoka Y, Nikaido T, Shimizu A, Honjo T. Structure of a rearranged gamma 1 chain gene and its implication to immunoglobulin class-switch mechanism. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2437–2441. [PMC free article] [PubMed]
  • Marcu KB, Lang RB, Stanton LW, Harris LJ. A model for the molecular requirements of immunoglobulin heavy chain class switching. Nature. 1982 Jul 1;298(5869):87–89. [PubMed]
  • Kim S, Davis M, Sinn E, Patten P, Hood L. Antibody diversity: somatic hypermutation of rearranged VH genes. Cell. 1981 Dec;27(3 Pt 2):573–581. [PubMed]
  • Fahrlander PD, Sümegi J, Yang JQ, Wiener F, Marcu KB, Klein G. Activation of the c-myc oncogene by the immunoglobulin heavy-chain gene enhancer after multiple switch region-mediated chromosome rearrangements in a murine plasmacytoma. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3746–3750. [PMC free article] [PubMed]
  • Gerondakis S, Cory S, Adams JM. Translocation of the myc cellular oncogene to the immunoglobulin heavy chain locus in murine plasmacytomas is an imprecise reciprocal exchange. Cell. 1984 Apr;36(4):973–982. [PubMed]
  • Kataoka T, Kawakami T, Takahashi N, Honjo T. Rearrangement of immunoglobulin gamma 1-chain gene and mechanism for heavy-chain class switch. Proc Natl Acad Sci U S A. 1980 Feb;77(2):919–923. [PMC free article] [PubMed]
  • Eckhardt LA, Birshtein BK. Independent immunoglobulin class-switch events occurring in a single myeloma cell line. Mol Cell Biol. 1985 Apr;5(4):856–868. [PMC free article] [PubMed]
  • Davis DD, Yoshida K, Kingsbury L, Sakano H. Circular DNA resulting from recombination between V-(D)-J joining signals and switch repetitive sequences in mouse thymocytes. J Exp Med. 1991 Mar 1;173(3):743–746. [PMC free article] [PubMed]
  • Shapira SK, Jabara HH, Thienes CP, Ahern DJ, Vercelli D, Gould HJ, Geha RS. Deletional switch recombination occurs in interleukin-4-induced isotype switching to IgE expression by human B cells. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7528–7532. [PMC free article] [PubMed]
  • Mills FC, Thyphronitis G, Finkelman FD, Max EE. Ig mu-epsilon isotype switch in IL-4-treated human B lymphoblastoid cells. Evidence for a sequential switch. J Immunol. 1992 Aug 1;149(3):1075–1085. [PubMed]
  • Shapira SK, Vercelli D, Jabara HH, Fu SM, Geha RS. Molecular analysis of the induction of immunoglobulin E synthesis in human B cells by interleukin 4 and engagement of CD40 antigen. J Exp Med. 1992 Jan 1;175(1):289–292. [PMC free article] [PubMed]
  • Shell BE, Collins JT, Elenich LA, Szurek PF, Dunnick WA. Two subfamilies of murine retrotransposon ETn sequences. Gene. 1990 Feb 14;86(2):269–274. [PubMed]
  • Katz A, Kahana C. Rearrangement between ornithine decarboxylase and the switch region of the gamma 1 immunoglobulin gene in alpha-difluoromethylornithine resistant mouse myeloma cells. EMBO J. 1989 Apr;8(4):1163–1167. [PMC free article] [PubMed]
  • Elenich LA, Dunnick WA. Sequence at insertion site of E.Tn retrotransposon into an immunoglobulin switch region suggests a role for switch recombinase. Nucleic Acids Res. 1991 Jan 25;19(2):396–396. [PMC free article] [PubMed]
  • Stanton LW, Yang JQ, Eckhardt LA, Harris LJ, Birshtein BK, Marcu KB. Products of a reciprocal chromosome translocation involving the c-myc gene in a murine plasmacytoma. Proc Natl Acad Sci U S A. 1984 Feb;81(3):829–833. [PMC free article] [PubMed]
  • Calame K, Kim S, Lalley P, Hill R, Davis M, Hood L. Molecular cloning of translocations involving chromosome 15 and the immunoglobulin C alpha gene from chromosome 12 in two murine plasmacytomas. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6994–6998. [PMC free article] [PubMed]
  • Stanton LW, Watt R, Marcu KB. Translocation, breakage and truncated transcripts of c-myc oncogene in murine plasmacytomas. Nature. 1983 Jun 2;303(5916):401–406. [PubMed]
  • Mowatt MR, Dunnick WA. DNA sequence of the murine gamma 1 switch segment reveals novel structural elements. J Immunol. 1986 Apr 1;136(7):2674–2683. [PubMed]
  • Gritzmacher CA, Liu FT. Expression of a recombinant murine IgE in transfected myeloma cells. J Immunol. 1987 Jan 1;138(1):324–329. [PubMed]
  • Scappino LA, Chu C, Gritzmacher CA. Extended nucleotide sequence of the switch region of the murine gene encoding immunoglobulin E. Gene. 1991 Mar 15;99(2):295–296. [PubMed]
  • Rudolph AK, Burrows PD, Wabl MR. Thirteen hybridomas secreting hapten-specific immunoglobulin E from mice with Iga or Igb heavy chain haplotype. Eur J Immunol. 1981 Jun;11(6):527–529. [PubMed]
  • Liu FT, Bohn JW, Ferry EL, Yamamoto H, Molinaro CA, Sherman LA, Klinman NR, Katz DH. Monoclonal dinitrophenyl-specific murine IgE antibody: preparation, isolation, and characterization. J Immunol. 1980 Jun;124(6):2728–2737. [PubMed]
  • Sanger F, Nicklen S, Coulson AR. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. [PMC free article] [PubMed]
  • Dunnick W, Shell BE, Dery C. DNA sequences near the site of reciprocal recombination between a c-myc oncogene and an immunoglobulin switch region. Proc Natl Acad Sci U S A. 1983 Dec;80(23):7269–7273. [PMC free article] [PubMed]
  • Schultz C, Petrini J, Collins J, Claflin JL, Denis KA, Gearhart P, Gritzmacher C, Manser T, Shulman M, Dunnick W. Patterns and extent of isotype-specificity in the murine H chain switch DNA rearrangement. J Immunol. 1990 Jan 1;144(1):363–370. [PubMed]
  • Hummel M, Berry JK, Dunnick W. Switch region content of hybridomas: the two spleen cell Igh loci tend to rearrange to the same isotype. J Immunol. 1987 May 15;138(10):3539–3548. [PubMed]
  • Siekevitz M, Kocks C, Rajewsky K, Dildrop R. Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses. Cell. 1987 Mar 13;48(5):757–770. [PubMed]
  • Fish S, Zenowich E, Fleming M, Manser T. Molecular analysis of original antigenic sin. I. Clonal selection, somatic mutation, and isotype switching during a memory B cell response. J Exp Med. 1989 Oct 1;170(4):1191–1209. [PMC free article] [PubMed]
  • Manser T. The intraclonal diversity and control of antibody isotype switch recombination. Int Immunol. 1990;2(9):893–902. [PubMed]
  • Shan H, Shlomchik M, Weigert M. Heavy-chain class switch does not terminate somatic mutation. J Exp Med. 1990 Aug 1;172(2):531–536. [PMC free article] [PubMed]
  • Feiss M, Fisher RA, Crayton MA, Egner C. Packaging of the bacteriophage lambda chromosome: effect of chromosome length. Virology. 1977 Mar;77(1):281–293. [PubMed]
  • Dunnick W, Stavnezer J. Copy choice mechanism of immunoglobulin heavy-chain switch recombination. Mol Cell Biol. 1990 Jan;10(1):397–400. [PMC free article] [PubMed]
  • Wuerffel R, Jamieson CE, Morgan L, Merkulov GV, Sen R, Kenter AL. Switch recombination breakpoints are strictly correlated with DNA recognition motifs for immunoglobulin S gamma 3 DNA-binding proteins. J Exp Med. 1992 Aug 1;176(2):339–349. [PMC free article] [PubMed]
  • Hertz GZ, Hartzell GW, 3rd, Stormo GD. Identification of consensus patterns in unaligned DNA sequences known to be functionally related. Comput Appl Biosci. 1990 Apr;6(2):81–92. [PubMed]
  • Schneider TD, Stormo GD, Gold L, Ehrenfeucht A. Information content of binding sites on nucleotide sequences. J Mol Biol. 1986 Apr 5;188(3):415–431. [PubMed]

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