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Derivation and diversification of monoclonal antibodies

Nobel lecture, 8 December 1984

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References

  1. Köhler G & Milstein C (1975) Continuous cultures of fused cells secreting antibodies of predefined specificity. Nature256, 995.

    Google Scholar 

  2. Köhler G & Milstein C (1976) Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. Eur. J. Immun.6, 511.

    Google Scholar 

  3. Polin RA (1980). Monoclonal antibodies against streptococcal antigens. In: Monoclonal Antibodies (Kenneth, McKearn & Bechtol, eds), pp 353–359, Plenum Press, New York.

    Google Scholar 

  4. Flamand A, Wiktor TJ & Koprowski H (1980) Use of hybridoma monoclonal antibodies in the detection of antigenic differences between rabies and rabies-related virus proteins. J. Gen. Virol.48, 97.

    Google Scholar 

  5. Mitchell G, Cruise KM, Garcia EG & Anders RF (1981) Hybridoma derived antibody with immunodiagnostic potential for schistosomiasis japonica. Proc. Nat. Acad. Sci. USA78, 3165.

    Google Scholar 

  6. Howard FD, Ledbetter JA, Wong J, Bieber C, Stinson EB & Herzenberg LA (1981) Human T lymphocyte differentiation marker defined by monoclonal antibodies that block E-rosette formation. J. Immunol.126, 2117.

    Google Scholar 

  7. Brodsky FM, Parham P, Barnstable CJ, Crumpton MJ & Bodmer WF (1979) Monoclonal antibodies for analysis of the HLA system. Immunol. Reviews47, 3.

    Google Scholar 

  8. Koprowski H, Steplewski Z, Herlyn D & Herlyn M (1978) Production of monoclonal antibody against human melanoma by somatic cell hybrids. Proc. Nat. Acad. Sci. USA75, 3405.

    Google Scholar 

  9. Secher DS & Burke DC (1980) A monoclonal antibody for large-scale purification of human leucocyte interferon. Nature285, 446.

    Google Scholar 

  10. McMaster WR & Williams AF (1979) Monoclonal antibodies to Ia antigens from rat thymus: Crossreactions with mouse and human and use in purification of rat Ia glycoproteins. Immunol. Reviews47, 117.

    Google Scholar 

  11. Miggiano V, Stähli C, Häring P, Schmidt J, Le Dain M, Glatthaar B & Staehlin T (1980). Monoclonal antibodies to three tumor markers: human chorionic gonadotropin, prostatic acid phosphatase and carcinoembryonic antigen. In: Protides of the Biological Fluids (Peters, ed), pp 501–504, Pergamon Press, Oxford.

    Google Scholar 

  12. Leptin M, Potash MJ, Grützmann R, Heusser C, Shulman M, Köhler G & Melchers F (1984) Monoclonal antibodies specific for murine IgM. I. Characterization antigenic determinants on the four constant domains of the μ chain. Eur. J. Immun.14, 554.

    Google Scholar 

  13. Yoshida N, Nussenzweig RS, Potocnjak P, Nussenzweig V & Aikawa M (1980) Hybridoma produces protective antibodies directed against the sporozoite stage of malaria parasite. Science207, 71.

    Google Scholar 

  14. Mudgett-Hunter M, Margolies MN, Smith TW, Nowotny J & Haber E (1980) Monoclonal antibodies to the cardiac glycoside digoxin. In: Monoclonal Antibodies and T Cell Hybridomas (Hämmerling G & Kearney J, eds), pp 367–374, Elsevier, Amsterdam.

    Google Scholar 

  15. Hollander N, Pillemer E & Weissman IL (1980) Blocking effect of Lyt-2 antibodies on T-cell functions. J. Exp. Med.152, 674.

    Google Scholar 

  16. Koskimies S (1980) Human lymphoblastoid cell line producing specific antibody against Rh-antigen D. Scand. J. Immunol.11, 73.

    Google Scholar 

  17. Reth M, Kelsoe G & Rajewsky K (1981) Idiotypic regulation by isologous monoclonal anti-idiotypic antibodies. Nature290, 257.

    Google Scholar 

  18. Holtkamp B, Cramer M, Lemke H & Rajewsky K (1981) Isolation of a cloned cell line expressing variant H2k using the fluorescence activated cell sorter. Nature289, 66.

    Google Scholar 

  19. Gerhard W & Webster RG (1978) Antigenic drift in influenza A virus. I. Selection and characterization of antigenic variants of A/PR/8/34 (HON1) influenza virus with monoclonal antibodies. J. Exp Med.148, 383.

    Google Scholar 

  20. Zipser B & McKay R (1981) Monoclonal antibodies distinguish identifiable neurones in the leech. Nature289, 549.

    Google Scholar 

  21. Mach JP, Buchegger F, Forni M, Ritchard J, Berche C, Lumbroso J-D, Schrejer M, Giradet Ch, Accolla RS & Carrel S (1981) Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintography. Immunology Today2, 239.

    Google Scholar 

  22. Coffino P & Scharff MD (1971) Rate of somatic mutation in immunoglobulin production by mouse myeloma cells. Proc. Nat. Acad. Sci. USA68, 219.

    Google Scholar 

  23. Morrison SL (1978) Murine heavy chain disease. Eur. J. Immun.8, 194.

    Google Scholar 

  24. Morrison SL (1979) Sequentially derived mutants of the constant region of the heavy chain of murine immunoglobulins. J. Immun.123, 793.

    Google Scholar 

  25. Mosmann TR & Williamson AR (1980) Structural mutations in a mouse immunoglobulin light chain resulting in failure to be secreted. Cell20, 283.

    Google Scholar 

  26. Wu GE, Hozumi N & Murialdo H (1983) Secretion of a λz immunoglobulin chain is prevented by a single amino acid substitution in its variable region. Cell33, 77.

    Google Scholar 

  27. Milstein C, Adetugbo K, Cowan NJ, Köhler G, Secher DS & Wilde CD (1977) Somatic cell genetics of antibody-secreting cells: Studies of clonal diversification and analysis by cell fusion. Cold Spring Harbor Symp. Quant. Biol.41, 793.

    Google Scholar 

  28. Neuberger MS & Rajewsky K (1981) Switch from hapten specific immunoglobulin M to immunoglobulin D secretion in a hybrid mouse cell line. Proc. Nat. Acad. Sci. USA78, 1138.

    Google Scholar 

  29. Radbruch A, Liesegang B, & Rajewsky K (1980) Isolation of variants of mouse myeloma X63 that express changed immunoglobulin class. Proc. Nat. Acad. Sci. USA77, 2909.

    Google Scholar 

  30. Sablitzky F, Radbruch A & Rajewsky K (1982) Spontaneous immunoglobulin class switching in myeloma and hybridoma cell lines differs from physiological class switching. Immun. Rev.67, 59.

    Google Scholar 

  31. Krawinkel V, Zoebelein G, Brüggemann M, Radbruch A & Rajewsky K (1983) Recombination between antibody heavy chain variable-region genes: evidence for gene conversion. Proc. Nat. Acad. Sci. USA80, 4997.

    Google Scholar 

  32. Cook WD & Scharff MD (1977) Antigen-binding mutants of mouse myeloma cells. Proc. Nat. Acad. Sci. USA74, 5687.

    Google Scholar 

  33. Rudikoff S, Giusti AM, Cook HD & Scharff MD (1982) Single amino acid substitution altering antigen-binding specificity. Proc. Nat. Acad. Sci. USA79, 1979.

    Google Scholar 

  34. Köhler G & Shulman M (1980) Immunoglobulin M mutants. Eur. J. Immun.10, 467.

    Google Scholar 

  35. Köhler G, Potash MJ, Lehrach H, & Shulman M (1982) Deletions in immunoglobulin mu chains. EMBO J.1, 555.

    Google Scholar 

  36. Hawley RG, Shulman JM, Murialdo H, Gibson DM & Hozumi N (1982) Mutant immunoglobulin genes have repetitive DNA elements inserted into their intervening sequences. Proc. Nat. Acad. Sci. USA79, 7425.

    Google Scholar 

  37. Sharon J, Gefter ML, Mauser T, Morrison SL, Oi VT & Ptashne M (1984) Expression of a VH-Ck chimaeric protein in mouse myeloma cells. Nature309, 364.

    Google Scholar 

  38. Köhler G, Baumann B, Iglesias A, McCubrey J, Potash MJ, Traunecker A & Zhu D (1984) Different ways to modify monoclonal antibodies. Med. Oncol & Tumor Pharmacother.1, 227.

    Google Scholar 

  39. Boulianne GL, Hozumi N & Shulman M (1984) Production of functional chimaeric mouse/human antibody. Nature312, 643.

    Google Scholar 

  40. Morrison SL, Johnson MJ, Herzenberg LA & Oi V (1984) Chimeric human antibody molecules: Mouse antigen binding domains with human constant region domains. Proc. Nat. Acad. Sci. USA81, 6851.

    Google Scholar 

  41. Neuberger MS, Williams GT & Fox RO (1984) Recombinant antibodies possessing novel effector functions. Nature312, 604.

    Google Scholar 

  42. Cobbold SP, Waldmann H (1984) Therapeutic potential of monovalent antibodies. Nature308, 460.

    Google Scholar 

  43. Milstein C & Cuello AC (1983) Hybrid hybridomas and their use in immunohistochemistry. Nature305, 537.

    Google Scholar 

  44. Köhler G (1980) Immunoglobulin chain loss in hybridoma lines. Proc. Nat. Acad. Sci. USA77, 2197.

    Google Scholar 

  45. Baumal R, Birshtein BK, Coffino P & Scharff MD (1973) Mutations in immunoglobulin-producing mouse myeloma cells. Science182, 164.

    Google Scholar 

  46. McHugh Y, Yagi M & Koshland ME (1981) The use of J and μ-chain analysis to assign lymphoid cell lines to various stages in B cell differentiation. In: B Lymphocytes in the Immune Response: Functional, Developmental and Interactive Properties (Klinman N, Mosier D, Scher I & Vitetta E, eds), p 467, Elsevier/North Holland, N.Y.

    Google Scholar 

  47. McKearn 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. Nat. Acad. Sci. USA81, 3180.

    Google Scholar 

  48. Sablitzky F, Wildner G & Rajewsky K (1985) Somatic mutation and clonal expansion of B cells in an antigen-driven immune response. EMBO J, in press.

  49. de Preval C & Fougereau M (1976) Specific interaction between VH and VL regions of human monoclonal immunoglobulins J. Mol. Biol.102, 657.

    Google Scholar 

  50. Klein M, Kostan C, Kells D & Dorrington K (1979) Biochemistry18, 1473.

    Google Scholar 

  51. Zhu D, Lefkovits I & Köhler G (1984) Frequency of expressed immunoglobulin light chain genes in lipopolysaccharide-stimulated Balb/c spleen cells. J. Exp. Med.160, 971.

    Google Scholar 

  52. Baumann B, Potash MJ & Köhler G (1984) Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse. EMBO J, in press.

  53. Kearney JF, Radbruch A, Liesegang B & Rajewsky K (1979) A new mouse myeloma cell line that has lost immunoglobulin expression but permits the construction of antibody-secreting hybrid cell lines. J. Immun.123, 1548.

    Google Scholar 

  54. Shulman MJ, Heusser C, Filkin C & Köhler G (1982) Mutations affecting the structure and function of immunoglobulin M. Molec. Cell. Biol.2, 1033.

    Google Scholar 

  55. Grosschedl R, Weaver D, Baltimore D & Constantini F (1984) Introduction of μ immunoglobulin gene into the mouse germ line. Specific expression in lymphoid cells and synthesis of functional antibody. Cell38, 647.

    Google Scholar 

  56. Brinster RL, Ritchie KA, Hammer RE, O'Brien RL, Arp B & Storb U (1983) Expression of a microinjected immunoglobulin gene in the spleen of transgenic mice. Nature306, 332.

    Google Scholar 

  57. Storb U, O'Brien RL, McMullen MD, Gollahon KA & Brinster RL (1984) High expression of cloned immunoglobulin κ gene in transgenic mice is restricted to B-lympocytes. Nature310, 238.

    Google Scholar 

  58. Ritchie KA, Brinster LR & Storb U (1984) Allelic exclusion and control of endogenous immunoglobulin gene rearrangement in transgenic mice. Nature312, 517.

    Google Scholar 

  59. Rusconi S & Köhler G (1985) A transgenic mouse line transmitting and expressing a specific pair of rearranged immunoglobulin μ and κ genes. Nature, in press.

  60. Alt WF, Yancopoulos GD, Blackwell KT, Wood C, Thomas E, Boss M, Coffmann R, Rosenberg N, Tonegawa S & Baltimore D (1984) Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J.3, 1209.

    Google Scholar 

  61. Kwan S, Max E, Seidman J, Leder P & Scharff M (1981) Two kappa immunoglobulin genes are expressed in the myeloma S107. Cell26, 57.

    Google Scholar 

  62. Hozumi N, Wu G, Murialdo H, Baumal R, Mosmann T, Winberry L & Marks A (1982) Arrangement of λ light chain genes in mutant clones of the MOPC31S mouse myeloma cells. J. Immunol.129, 260.

    Google Scholar 

  63. Shulman M, Wilde DC & Köhler G (1978) A better cell line for making hybridomas secreting specific antibodies. Nature276, 269–270.

    Google Scholar 

  64. Szybalski W, Szybalska EH & Ragni G (1962) Genetic studies with human cell lines. Natn. Cancer Inst. Monogr.7, 75–89.

    Google Scholar 

  65. Littlefield JW (1964) Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants. Science145, 709.

    Google Scholar 

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Köhler, G. Derivation and diversification of monoclonal antibodies. Biosci Rep 5, 533–549 (1985). https://doi.org/10.1007/BF01117066

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