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Transcription Targets Recombination at Immunoglobulin Switch Sequences in a Strand-Specific Manner

  • Chapter
Molecular Analysis of DNA Rearrangements in the Immune System

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 217))

Abstract

Immunoglobulin (lg) heavy chain gene assembly can be divided into two developmentally and mechanistically distinct phases during B cell maturation. The initial, antigen-independent phase occurs primarily in the bone marrow and is catalyzed by the V(D)J recombination activity The second, primarily antigen-dependent phase involves a second type of gene rearrangement termed class switch recombination. A major mechanism of isotype switching is directed DNA recombination (Davis et al. 1980; Schwedler et al. 1990). Class switch recombination takes place in the peripheral lymphoid tissues and replaces the initial constant regions, Cμ and Cδ, with any of several downstream constant regions (for reviews, see Coffman et al. 1993; Gritzmacher 1989). By changing antibody class, or isotype, the same antigen specificity can be associated with a variety of effector functions.

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References

  • Burrows PD, Beck-Engeser GB, Wabi MR (1983) Immunoglobulin heavy-chain class switching in a pre-B cell line is accompanied by DNA rearrangement. Nature 306:243–246

    Article  PubMed  CAS  Google Scholar 

  • Clark DJ, Felsenfeld G (1992) A nucleosome core is transferred out of the path of a transcribing polymerase. Cell 71:11–22

    Article  PubMed  CAS  Google Scholar 

  • Coffman RL, Lebman DA, Rothman P (1993) Mechanism and regulation of immunoglobulin isotype switching. Adv Immunol 54:229–270

    Article  PubMed  CAS  Google Scholar 

  • Daniels GA, Lieber MR (1995) Strand-specificity in the transcriptional targeting of recombination at immunoglobulin class switch sequences. Proc Natl Acad Sci USA 92:5625–5629

    Article  PubMed  CAS  Google Scholar 

  • Davis M, Kim SK, Hood LE (1980) DNA sequences mediating class switching in a-immunoglobulins. Science 209:1360–1365

    Article  PubMed  CAS  Google Scholar 

  • Davis MM, Kim SK, Hood L (1980) Immunoglobulin class switching: developmentally regulated DNA rearrangements during differentiation. Cell 22:1–2

    Article  PubMed  CAS  Google Scholar 

  • DePinho R, Kruger K, Andrews N, Lutzker S, Baltimore D, Alt FW (1984) Molecular basis of heavy- chain class switching and switch region deletion in an Abelson virus-transformed cell line. Mol Cell Biol 4:2905–2910

    PubMed  CAS  Google Scholar 

  • Dunnick WA, Hertz GZ, Scappino L, Gritzmacher C (1993) DNA sequence at immunoglobulin switch region recombination sites. NucI Acid Res 21:365–372

    Article  CAS  Google Scholar 

  • Gerstein RM, Frankel WN, Hsieh C-L, Durdik JM, Rath S, Coffin JM, Nisonoff A, Scising E (1990) Isotype switching of an immunoglobulin heavy chain transgene occurs by DNA recombination between different chromosomes. Cell 63:537–548

    Article  PubMed  CAS  Google Scholar 

  • Gritzmacher CA (1989) Molecular aspects of heavy-chain class switching. Crit Rev Immunol 9:173–200

    PubMed  CAS  Google Scholar 

  • Gu H, Zou Y-R, Rajewsky K (1993) Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting. Cell 73:1155–1164

    Article  PubMed  CAS  Google Scholar 

  • Hesse JE, Lieber ML, Geliert M, Mizuuchi K (1987) Extrachromosomal substrates undergo inversion or deletion at immunoglobulin VDJ joining signals. Cell 49:775–783

    Article  PubMed  CAS  Google Scholar 

  • Jack HM, McDowell M, Steinberg CM, Wabi M (1988) Looping out and deletion mechanism for the immunoglobulin heavy-chain class switch. Proc Natl Acad Sci 85:1581–1585

    Article  PubMed  CAS  Google Scholar 

  • Jung S, Rajewsky K, Radbruch A (1993) Shutdown of class switch recombination by deletion of a switch region control element. Science 259:984–987

    Article  PubMed  CAS  Google Scholar 

  • Lepse CL, Kumar R, Ganea D (1994) Extrachromosomal eukaryotic DNA substrates for switch recombination: analysis of isotype and cell specificity DNA. Cell Biol 13:1151–61

    CAS  Google Scholar 

  • Leung H, Maizels N (1992) Transcriptional regulatory elements stimulate recombination in extrachromosomal substrates carrying immunoglobulin switch-region sequences. Proc Natl Acad Sci 89:4154–4158

    Article  PubMed  CAS  Google Scholar 

  • Leung H, Maizels N (1994) Regulation and targeting of recombination in extrachromosomal substrates carrying immunoglobulin switch region sequences. Mol Cell Biol 14:1450–1458

    PubMed  CAS  Google Scholar 

  • Liao R, Giannini SL, Birshtein BK (1992) A nuclear DNA-binding protein expressed during early stages of B cell differentiation interacts with diverse segments within and 3’ of the Ig H chain gene cluster J Immunol 148:2909–2917

    PubMed  CAS  Google Scholar 

  • Lieber ML, Hesse JE, Mizuuchi K, Geliert M (1987) Developmental stage specificity of the lymphoid V(D)J recombination activity Genes Dev 1:751–761

    Article  PubMed  CAS  Google Scholar 

  • Lutzker SG, Alt FW (1989) Immunoglobulin heavy-chain class switching. In: Berg DE, Howe MM (eds) Mobile DNA. American Society for Microbiology Washington, DC, pp 693–714

    Google Scholar 

  • Marcu KB, Banerji J, Penncavage NA, Lang R, Arnheim N (1980) 5’ flanking region of immunoglobulin heavy chain constant region genes display length heterogeneity in germlines of inbred mouse strains. Cell 22:187–196

    Article  PubMed  CAS  Google Scholar 

  • Ott DE, Alt FW, Marcu KB (1987) Immunoglobulin heavy chain switch region recombination within a retroviral vector in murine pre-B cells. EMBO 6:577–584

    CAS  Google Scholar 

  • Petrini J, Dunnick W (1989) Products and implied mechanism of H chain switch recombination. J Immunol 142:2932–2935

    PubMed  CAS  Google Scholar 

  • Reaban ME, Griffin JA (1990) Induction of RNA-stabilized DNA conformers by transcription of an immunoglobulin switch region. Nature 348:342–344

    Article  PubMed  CAS  Google Scholar 

  • Schwedler UV, Jack H-M, Wabi M (1990) Circular DNA is a product of the immunoglobulin class switch rearrangement. Nature 345:452–456

    Article  Google Scholar 

  • Stavnezer J, Abbott J, Sirlin S (1984) Immunoglobulin heavy chain switching in culture 129 murine B lymphoma cells:commitment to an IgA or IgE switch. Curr Topics Microbiol Immunol 113:109–115

    Article  CAS  Google Scholar 

  • Stavnezer J, Radcliff G, Lin Y-C, Nietupski J, Berggren L, Sitia R, Severinson E (1988) Immunoglobulin heavy-chain switching may be directed by prior induction of transcripts from constant-region genes. Proc Natl Acad Sci USA 85:7704–7708

    Article  PubMed  CAS  Google Scholar 

  • Stavnezer-Nordgren J, Sirlin S (1986) Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching EMBO 5:95–102

    CAS  Google Scholar 

  • Sugiyama H, Maeda T Akira S, Kishimoto S (1986) Class-switching from to y3 or Y2b production at pre-B cell stage. J Immunol 136:3092–3097

    PubMed  CAS  Google Scholar 

  • Szurek F, Petrini J, Dunnick W (1985) Complete nucleotide sequence of the murine y3 switch region and analysis of switch recombination sites in twoyS-expressing hybridomas. J Immunol 135:620–626

    PubMed  CAS  Google Scholar 

  • Waters SH, Saikh KU, Stavnezer J (1989) A B-cell-specific nuclear protein that binds to DNA sites 5’ to immunoglobulin Sa tandem repeats is regulated during differentiation. Mol Cell Biol 9:5594–5601

    PubMed  CAS  Google Scholar 

  • White MB, Word CJ, Humphries CG, Blattner FR, Tucker PW (1990) Immunoglobulin D switching can occur through homologous recombination in human B cells. Mol Cell Biol 10:3690–3699

    PubMed  CAS  Google Scholar 

  • Williams M, Maizels N (1991) LR1, a lipopolysacharide-responsive factor with binding sites in the immunoglobulin switch regions and heavy-chain enhancer. Genes Dev 5:2353–2361

    Article  PubMed  CAS  Google Scholar 

  • Wuerffel R, Jamieson CE, Morgan L, Merkulov GV, Sen R, Kenter AL (1992) Switch recombination breakpoints are strictly correlated with DNA recognition motifs for immunoglobulin S73 DNA- binding proteins J Exp Med 176:339–349

    Article  PubMed  CAS  Google Scholar 

  • Xu U, Gorham B, Li SC, Bottaro A, Alt FA, Rothman P (1993) Replacement of germ-line e promoter by gene targeting alters control of immunoglobulin heavy chain class switching. Proc Natl Acad Sci 90:3705–3709

    Article  PubMed  CAS  Google Scholar 

  • Xu M, Stavnezer J (1992) Regulation of transcription of immunoglobulin germ-line gl RNA: analysis of the promoter/enhancer. EMBO 11:145–155

    CAS  Google Scholar 

  • Yancopoulos GD, DePinho RA, Zimmerman KA, Lutzker SG, Rosenberg N, Alt FW (1986) Secondary genomic rearrangement events in pre-B cells: VhDJh replacement by a LINE-1 sequence and directed class switching. EMBO 5:3259–3266

    CAS  Google Scholar 

  • Yasui H, Akahori Y Hirano M, Yamada K, Kurosawa Y (1989) Class switch from jx to 5 is mediated by homologous recombination between sequences in human immunoglobulin gene loci. Eur J Immunol 19:1399–1403

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Bottaro A, Li S, Stewart V Alt F (1993) A selective defect in lgG2b switching as a result of targeted mutation of the lY2b promoter and exon. EMBO J 12:3529–3537

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Molecular Oncology, Departments of Pathology, Medicine, and Biochemistry, Washington University School of Medicine, 660 S. Euclid Ave., Box 8118, 63110, St. Louis, MO, USA

    Gregory A. Daniels

Authors
  1. Gregory A. Daniels
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  2. Michael R. Lieber
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Editor information

Editors and Affiliations

  1. Institute for Immunology, Grenzacherstr. 487, CH-4005, Basel, Switzerland

    Rolf Jessberger

  2. Division of Molecular Oncology, Department of Pathology, Washington University School of Medicine, Campus Box 8118, 660 So. Euclid Ave., 63110, St. Louis, MO, USA

    Michael R. Lieber

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© 1996 Springer-Verlag Berlin Heidelberg

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Daniels, G.A., Lieber, M.R. (1996). Transcription Targets Recombination at Immunoglobulin Switch Sequences in a Strand-Specific Manner. In: Jessberger, R., Lieber, M.R. (eds) Molecular Analysis of DNA Rearrangements in the Immune System. Current Topics in Microbiology and Immunology, vol 217. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-50140-1_12

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  • DOI: https://doi.org/10.1007/978-3-642-50140-1_12

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-50142-5

  • Online ISBN: 978-3-642-50140-1

  • eBook Packages: Springer Book Archive

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