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Somatic Hypermutability

  • Chapter
Book cover Molecular Analysis of DNA Rearrangements in the Immune System

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

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Abstract

In his book “What is life?” which was so influential at the tinne, Erwin Schrödinger (1944) mused, “In orderte be suitable material for the work of natural selection, mutations must be rare events.” That is, stability is one of the most important properties of the gene. A decade and a half later, the visionary Joshua Lederberg (1959) was musing about the origin of antibody diversity. He proposed that the instability of genes, i.e., from somatic mutation, was crucial in this process.

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References

  • Allegrucci M, Young-Cooper GO, Alexander CB, Newman BA, Mage RG (1991) Preferential rearrangement in normal rabbits of the 3’ VHa allotype gene that is deleted in Alicia mutants; somatic hypermutation conversion may play a major role in generating the heterogeneity of rabbit heavy chain variable region sequences. Eur J Immunol 21:411–417

    Article  PubMed  CAS  Google Scholar 

  • Bachi J, Wabi M (1995) Hypermutation in T cells questioned. Nature 375:285–286

    Article  CAS  Google Scholar 

  • Bachi J, Wabi M (1996) An immunoglobulin mutator that preferentially targets G-C base pairs. Proc Natl Acad Sci USA 93:851–855

    Article  Google Scholar 

  • Baker SM, Bronner CE, Zhang L, Plug AW, Robatzek M, Warren G, Elliott EAYJ, Ashley T, Arnheim N, Flavell RA, Liskay RM (1995) Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82:309–319

    Article  PubMed  CAS  Google Scholar 

  • Baumal R, Birshtein BK, Coffino P, Scharff MD (1973) Mutations in immunoglobulin-producing mouse myeloma cells. Science 182:164–166

    Article  PubMed  CAS  Google Scholar 

  • Berek C, Milstein C (1987) Mutation drift and repertoire shift in the maturation of the immune response. Immunol Rev 96:23–41

    Article  PubMed  CAS  Google Scholar 

  • Berek C, Griffiths GM, Milstein C (1985) Molecular events during maturation of the immune response to oxazolone. Nature 316:412–418

    Article  PubMed  CAS  Google Scholar 

  • Berinstein N, Campbell MJ, Lam K, Carswell C, Levy S, Levy R (1990) Idiotypic variation in a human B lymphoma cell line. J Immunol 144:752–758

    PubMed  CAS  Google Scholar 

  • Bernard O, Hozumi N, Tonegawa S (1978) Sequences of mouse immunoglobulin light chain genes before and after somatic changes. Cell 15:1133–1144

    Article  PubMed  CAS  Google Scholar 

  • Betz AG, Rada C, Pannell R, Milstein C, Neubörger MS (1993) Passenger transgenes reveal intrinsic specificity of the antibody hypermutation mechanism: clustering, polarity and specific hotspots. Proc Natl Acad Sci USA 90:2385–2388

    Article  PubMed  CAS  Google Scholar 

  • Betz AG, Milstein C, Gonzalez-Fernandez A, Pannell R, Larson T, Neubörger MS (1994) Elements regulating somatic hypermutation of an immunoglobulin kappa gene: critical role for the intron enhancer/matrix attachment region. Cell 77:239–248

    Article  PubMed  CAS  Google Scholar 

  • Bothwell ALM, Paskind M, Reth M, Imanishi-Kari T, Rajewsky K, Baltimore D (1981) Heavy chain variable region contribution to the NPb family of antibodies:somatic mutation evident in a gamma 2a variable region. Cell 24:625–637

    Article  PubMed  CAS  Google Scholar 

  • Brenner S, Milstein C (1966) Origin of antibody variation. Nature 211:242–243

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Roberts VA, Rittenberg MB (1992) Generation and analysis of random point mutations in an antibody CDR2 sequence: many mutated antibodies lose their ability to bind antigen. J Exp Med 176:855–866

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Nagy Z, Radic MZ, Hardy RR, Huszar D, Camper SA, Weigert M (1995) The site and stage of anti-DNA B-cell deletion. Nature 373:252–255

    Article  PubMed  CAS  Google Scholar 

  • Clarke SH, Huppi K, Ruezinsky D, Staudt L, Gerhard W, Weigert M (1985) Inter- and intraclonal diversity in the antibody response to influenza hennagglutinin. J Exp Med 161:687–704

    Article  PubMed  CAS  Google Scholar 

  • Coffino P, Scharff MD (1971) Rate of sonnatic mutation in immunoglobulin production by mouse myeloma cells. Proc Natl Acad Sci USA 68:219–223

    Article  PubMed  CAS  Google Scholar 

  • Crews S, Griffin J, Huang H, Calame K, Hood L (1981) A single VH gene segment encodes the immune response to phosphorylcholine:somatic mutation is correlated with the class of the antibody Cell 25:59–704

    Article  PubMed  CAS  Google Scholar 

  • Cunningham AJ, Fordham SA (1974) Antibody cell daughters can produce antibody of different specificities. Nature 250:669–671

    Article  PubMed  CAS  Google Scholar 

  • Desiderio SV Yancopoulos GD, Paskind M, Thomas E, Boss MA, Landau N, Alt FW, Baltimore D (1984) Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature 311:752–755

    Article  PubMed  CAS  Google Scholar 

  • Du Pasquier L (1993) Phylogeny of B-cell development. Curr Biol 5:185–193

    Google Scholar 

  • Eigen M (1993) Viral quasi-species. Sci Am 269:42–49

    Article  PubMed  CAS  Google Scholar 

  • Gay D, Saunders T Camper S, Weigert M (1993) Receptor editing: an approach by autoreactive B cells to escape tolerance. J Exp Med 177:999–1008

    Article  PubMed  CAS  Google Scholar 

  • Gearhart PJ (1993) Somatic mutation and affinity maturation. In: Paul WE (ed) Fundamental immunology, 3rd edn. Raven, New York, pp 865–885

    Google Scholar 

  • Gearhart PJ, Bogenhagen, DF (1983) Clusters of point mutations are found exclusively around rearranged antibody variable genes. Proc Natl Acad Sci USA 80:3439–3443

    Article  PubMed  CAS  Google Scholar 

  • Gearhart PJ, Johnson ND, Douglas R, Hood L (1981). IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts. Nature 291:29–34

    Article  PubMed  CAS  Google Scholar 

  • Gershenfeld HK, Tsukamato A, Weissman IL, Joho R (1981) Somatic diversification is required to generate VK genes of M0PC511 and MOPC167 myeloma proteins. Proc Natl Acad Sci USA 78:7674–7678

    Article  PubMed  CAS  Google Scholar 

  • Gonzalez-Fernandez A, Gupta SK, Pannell R, Neubörger MS, Milstein C (1994) Somatic mutation of immunoglobulin lambda chains: a segment of the major intron hypermutates as much as the complementarity-determining regions. Proc Natl Acad Sci USA 91:12614–12618

    Article  PubMed  CAS  Google Scholar 

  • Goodnow CC (1992) Transgenic mice and analysis of B-cell tolerance. Ann Rev Immunol 10:489–518

    Article  CAS  Google Scholar 

  • Goodnow CC, Crosbie J, Jorgensen H, Brink RA, Basten A (1989) Induction of self-tolerance in mature peripheral B lymphocytes. Nature 342:385–391

    Article  PubMed  CAS  Google Scholar 

  • Green NS, Rabinowitz JL, Zhu M, Kobrin BJ, Scharff MD (1995) Immunoglobulin variable region hypermutation in hybrids derived from a pre-B- and a myeloma cell line. Proc Natl Acad Sci USA 92:6304–6308

    Article  PubMed  CAS  Google Scholar 

  • Griffiths GM, Berek C, Kaartinen M, Milstein C (1984) Somatic mutation and the maturation of immune response to 2-phenyloxazolone. Nature 312:271–275

    Article  PubMed  CAS  Google Scholar 

  • Grossehedl R, Baltimore D (1985) Cell-type specificity of immunoglobulin gene expression is regulated by at least three DNA sequence elements. Cell 41:885–897

    Article  Google Scholar 

  • Gu H, Tarlinton D, Muller W, Rajewsky K, Forster I (1991) Most peripheral B cells in mice are ligand selected. J Exp Med 173:1357–1371

    Article  PubMed  CAS  Google Scholar 

  • Hanawalt PC (1994) Transcription-coupled repair and human disease. Science 266:1957–1958

    Article  PubMed  CAS  Google Scholar 

  • Harriman W, Volk H, Defranoux N, Wabi M (1993) Immunoglobulin class switch recombination. Annu Rev Immunol 11:361–384

    Article  PubMed  CAS  Google Scholar 

  • Hartley SB, Crosbie J, Brink R, Kantor AB, Basten A, Goodnow CC (1991) Elimination from peripheral lymphoid tissues of self-reactive B lymphocytes recognizing membrane-bound antigens. Nature 353:765–769

    Article  PubMed  CAS  Google Scholar 

  • Hengstschlager M, Williams M, Maizels N (1994) A lambda 1 transgene under the control of a heavy chain promoter and enhancer does not undergo somatic hypermutation. Eur J Immunol 24:1649–1656

    Article  PubMed  CAS  Google Scholar 

  • Hinds-Frey KR, Nishikata H, Litman RX Litman GW (1993) Somatic variation precedes extensive diversification of germline sequences and combinatorial joining in the evolution of immunoglobulin heavy chain diversity J Exp Med 178:815–824

    Article  PubMed  CAS  Google Scholar 

  • Jäck HM, Wabi M (1987). High rates of deletions in the constant region segment of the immunoglobulin mu gene. Proc Natl Acad Sci USA 84:4934–4938

    Article  PubMed  Google Scholar 

  • Jacob J, Kelsoe G (1992) In situ studies of the primary immune response to (4-hydroxy-3-nitrophe- nyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers. J Exp Med 176:679–687

    Article  PubMed  CAS  Google Scholar 

  • Jacob J, Kelsoe G, Rajewsky K, Weiss U (1991) Intraclonal generation of antibody mutants in germinal centres. Nature 354:389–392

    Article  PubMed  CAS  Google Scholar 

  • Jacob J, Przylepa J, Miller C, Kelsoe G (1993) In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. III. The kinetics of V region mutation and selection in germinal center B cells. J Exp Med 178:1293–307

    Article  PubMed  CAS  Google Scholar 

  • Jerne NK (1971) The somatic generation of immune recognition. Eur J Immunol 1:1–9

    Article  PubMed  CAS  Google Scholar 

  • Kelsoe G, Zheng B (1993) Sites of B-cell activation in vivo. Curr Opin Immunol 5:418–422

    Article  PubMed  CAS  Google Scholar 

  • Kim S, Davis M, Sinn E, Patten R Hood L (1981) Antibody diversity: somatic hypermutation of rearranged VH genes. Cell 27:573–581

    Article  PubMed  CAS  Google Scholar 

  • Knight KL, Becker RS (1990) Molecular basis of the allelic inheritance of rabbit immunoglobulin VH allotypes:implications for the generation of antibody diversity Cell 60:963–970

    Article  PubMed  CAS  Google Scholar 

  • Knight KL, Becker RS, DiPietro LA (1991) Restricted utilization of germ-line VH genes in rabbits:im- plications for inheritance of VH allotypes and generation of antibody diversity. Adv Exp Med Biol 292:235–424

    Article  PubMed  CAS  Google Scholar 

  • Küppers R, Zhao M, Hansmann ML, Rajewsky K (1993) Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J 12:4955–4967

    PubMed  Google Scholar 

  • Küppers R, Rajewsky K, Zhao M, Simons G, Laumann R, Fischer R, Hansmann ML (1994) Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development. Proc Natl Acad Sci USA 91:10962–10966

    Article  PubMed  Google Scholar 

  • Lederberg J (1959). Genes and antibodies. Do antigens bear instructions for antibody specifity or do they select cell lines that arise by mutation? Science 129:1649–1653

    Article  PubMed  CAS  Google Scholar 

  • Levy S, Mendel E, Kon S, Avnur Z, Levy R (1988) Mutational hot spots in Ig V region genes of human follicular lymphomas. J Exp Med 168:475–89

    Article  PubMed  CAS  Google Scholar 

  • Lieber MR (1992) The mechanism of V(D)J recombination: a balance of diversity specificity, and stability Cell 70:873–876

    Article  PubMed  CAS  Google Scholar 

  • Linton PJL, Decker DJ, Klinman NR (1989) Primary antibody-forming cells and secondan/ B cells are generated from separate precursor cell subpopulations. Cell 59:1049–1059

    Article  Google Scholar 

  • Maizels N (1989) Might gene conversion be the mechanism of somatic hypermutation of mammalian immunoglobulin genes? Trends Genet 5:4–8

    Article  PubMed  CAS  Google Scholar 

  • Manser T (1990) The efficiency of antibody affinity maturation:can the rate of B-cell division be limiting? Immunol Today 11:305–308

    Article  PubMed  CAS  Google Scholar 

  • Manser T, Huang SY, Gefter ML (1984) Influence of clonal selection on the expression of immunoglobulin variable region genes. Science 226:1283–1288

    Article  PubMed  CAS  Google Scholar 

  • McKean D, Huppi K, Bell M, Staudt L, Gerhard W, Weigert M (1984) Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin. Proc Natl Acad Sci USA 81:3180–3184

    Article  PubMed  CAS  Google Scholar 

  • Meyer J, Jäck HM, Ellis N, Wabi M (1986) High rate of somatic point mutation in vitro in and near the variable-region segment of an immunoglobulin heavy chain gene. Proc Natl Acad Sci USA 83:6950–6953

    Article  PubMed  CAS  Google Scholar 

  • Milstein C, Adetugbo K, Cowan NJ, Kohier G, Secher DS (1978) Expression of antibody genes in tissue culture:structural mutants and hybrid cells. National Cancer Institute Monographs 48:321–330

    Google Scholar 

  • Nemazee D (1993) Promotion and prevention of autoimmunity by B lymphocytes. Curr Opin Immunol 5:866–72

    Article  PubMed  CAS  Google Scholar 

  • Radic MZ, Erikson J, Litwin S, Weigert M (1993) B lymphocytes may escape tolerance by revising their antigen receptors. J Exp Med 177:1165–1173

    Article  PubMed  CAS  Google Scholar 

  • Reynaud CA, Anquez V Grimal H, Weill JC (1987) A hyperconversion mechanism generates the chicken light chain preimmune repertoire. Cell 48:379–88

    Article  PubMed  CAS  Google Scholar 

  • Reynaud CA, Dahan A, Anquez V Weill JC (1989) Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region. Cell, 59:171–183

    Article  PubMed  CAS  Google Scholar 

  • Reynaud CA, Mackay CR, Muller RG, Weill JC (1991) Somatic generation of diversity in a mammalian primary lymphoid organ:the sheep ileal Peyer’s patches. Cell 64:995–1005

    Article  PubMed  CAS  Google Scholar 

  • Reynaud CA, Garcia C, Hein WR, Weill JC (1995) Hypermutation generating the sheep immunoglobulin repertoire is an antigen-independent process. Cell 80:115–125

    Article  PubMed  CAS  Google Scholar 

  • Ritchie KA, Brinster RL, Storb U (1984) Allelic exclusion and control of endogenous immunoglobulin gene rearrangement in kappa transgenic mice. Nature 312:517–520

    Article  PubMed  CAS  Google Scholar 

  • Rogerson B, Hackett J Jr, Peters A, Haasch D, Storb U (1991) Mutation pattern of immunoglobulin transgenes is compatible with a model of somatic hypermutation in which targeting of the mutator is linked to the direction of DNA replication. EMBO J 10:4331–4341

    PubMed  CAS  Google Scholar 

  • Rogozin IB, Kolchanov NA (1992) Somatic hypermutagenesis in immunoglobulin genes. II. Influence of neighbouring base sequences on mutagenesis. Biochim Biophys Acta 1171:11–18

    PubMed  CAS  Google Scholar 

  • Rudikoff S, Pawlita M, Pumphrey J, Heller M (1984) Somatic diversification of immunoglobulins. Proc Natl Acad Sci USA 81:2162–2165

    Article  PubMed  CAS  Google Scholar 

  • Russell DM, Dembic Z, Morahan G, Miller JF; Burki K, Nemazee D (1991) Peripheral deletion of self-reactive B cells. Nature 354:308–311

    Article  PubMed  CAS  Google Scholar 

  • Sablitzky F, Wildner G, Rajewsky K (1985) Somatic mutation and clonal expansion of B cells in an antigen-driven immune response. EMBO J. 4:345–350

    PubMed  CAS  Google Scholar 

  • Scharff MD, Aguila HL, Behar SM, Chien NC, DePinho R, French DL, Pollock RR, Shin SU (1987) Studies on the somatic instability of immunoglobulin genes in vivo and in cultured cells. Immunol Rev 96:75–90

    Article  PubMed  CAS  Google Scholar 

  • Schrödinger E (1944) What is life? Cambridge University Press, Cambridge Scising E, Storb U (1981) Somatic mutation of immunoglobulin light-chain variable-region genes. Cell 25:47–58

    Google Scholar 

  • Sharpe MJ, Milstein C, Jarvis JM, Neuberger MS (1991) Somatic hypermutation of immunoglobulin K L chain may depend on sequences 3’ of C kappa and occurs on passenger transgenes. EMBO J 10:2139–2145

    PubMed  CAS  Google Scholar 

  • Shokat KM, Goodnow CC (1995) Antigen-induced B-cell death and elimination during germinal-centre immune responses. Nature 375:334–338

    Article  PubMed  CAS  Google Scholar 

  • Siekevitz M, Kocks C, Rajewsky K, Dildrop R (1987) Analysis of somatic mutation and class switching in naive and memory B cells generating adoptive primary and secondary responses. Cell 48:757–770

    Article  PubMed  CAS  Google Scholar 

  • Sprent J (1994) T and B memory cells. Cell 76:315–322

    Article  PubMed  CAS  Google Scholar 

  • Tiegs SL, Russell DM, Nemazee D (1993) Receptor editing in self-reactive bone marrow B cells. J Exp Med 177:1009–1020

    Article  PubMed  CAS  Google Scholar 

  • Thompson CB, Neimen PE (1987) Somatic diversification of the chicken immunoglobulin light chain gene is limited to the rearranged variable gene segment. Cell 48:369–378

    Article  PubMed  CAS  Google Scholar 

  • Umar A, Schweitzer PA, Levy NS, Gearhart JD, Gearhart PJ (1991) Mutation in a reporter gene depends on proximity to and transcription of immunoglobulin variable transgenes. Proc Natl Acad Sci USA 88:4902–4906

    Article  PubMed  CAS  Google Scholar 

  • Vescio RA, Cao J, Hong CH, Lee JC, Wu CH, Der Danielian M, Wu V Newman R, Lichtenstein AK, Berenson, J (1995) Myeloma Ig heavy chain region sequences reveal prior antigenic selection and marked somatic mutation but no intraclonal diversity J Immunol 155:2487–2497

    PubMed  CAS  Google Scholar 

  • von Borstel RC, Cain KT, Steinberg C (1971) Inheritance of spontaneous mutability in yeast. Genetics 69:17–27

    Google Scholar 

  • Wabi M, Burrows PD, von Gabain A, Steinberg C (1985) Hypermutation at the immunoglobulin heavy chain locus in a pre-B-cell line. Proc Natl Acad Sci USA 82:479–482

    Article  Google Scholar 

  • Wabi M, Jäck HM, Meyer J, Beck-Engeser G, von Borstel R, Steinberg C (1987) Measurements of mutation rates in B lymphocytes. Immunol Rev 96:91–107

    Article  Google Scholar 

  • Wabi M, Harriman W, Fischer E, Steinberg C (1994) Can we outlive Methuselah? Cybernet Sys 25:373–387

    Article  Google Scholar 

  • Weigert MG, Cesari IM, Yonkovich SJ, Cohn M (1970) Variability in the lambda light chain sequences of mouse antibody Nature 228:1045–1047

    Article  PubMed  CAS  Google Scholar 

  • Weinstein PD, Anderson AO, Mage RG (1994) Rabbit IgH sequences in appendix germinal centers:VH diversification by gene conversion-like and hypermutation mechanisms. Immunity 1:647–659

    Article  PubMed  CAS  Google Scholar 

  • Wilson M, Hsu E, Marcuz A, Courtet M, Du Pasquier L, Steinberg C (1992) What limits affinity maturation of antibodies in Xenopus — the rate of somatic mutation or the ability to select mutants? EMBO J 11:4337–4347

    PubMed  CAS  Google Scholar 

  • Wilson M, Marcuz A, Du Pasquier L (1995) Somatic mutations during an immune response in Xenopus tadpoles. Dev Immunol (in press)

    Google Scholar 

  • Xu B, Scising E (1994) Analysis of sequence transfers resembling gene conversion in a mouse antibody transgene. Science 265:1590–1593

    Article  PubMed  CAS  Google Scholar 

  • Yelamos J, Klix N, Goyenechea B, Lozano F, Chui YL, Gonzalez-Fernandez A, Panell R, Neuberger MS, Milstein C (1995) Targeting of non-lg sequences in place of the V segment by somatic hypermutation. Nature 376:225–229

    Article  PubMed  CAS  Google Scholar 

  • Zhang LH, Vrieling H, van Zeeland AA, Jenssen D (1992) Spectrum of spontaneously occurring mutations in the hprt gene of V79 Chinese hamster cells. J Mol. Biol 223:627–635

    Article  PubMed  CAS  Google Scholar 

  • Zheng B, Xue W, Kelsoe G (1994) Locus-specific somatic hypermutation in germinal centre T cells. Nature 372:556–559

    Article  PubMed  CAS  Google Scholar 

  • Zhu M, Rabinowitz JL, Green NS, Kobrin BJ, Scharff MD (1995) A well-differentiated B-cell line is permissive for somatic mutation of a transfected immunoglobulin heavy-chain gene. Proc Natl Acad Sci USA 92:2810–2814

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Microbiology and Immunology, University of California, 94143-0670, San Francisco, CA, USA

    Matthias Wabl

  2. Basel Institute for Immunology, Postfach 4005, Basel, Switzerland

    Charles Steinberg

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  1. Matthias Wabl
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  2. Charles Steinberg
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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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Wabl, M., Steinberg, C. (1996). Somatic Hypermutability. 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_14

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