Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Human Monoclonal Antibodies as Probes to Study Autoimmune and Allergic Disorders

Bio/Technology volume 4, pages 210–218 (1986)Cite this article

Abstract

The ability to generate monoclonal antibodies (Mabs) of defined antigenic specificity has revolutionized modern medicine. Although the technology for the generation of human monoclonal antibodies is clearly still behind that available in rodent systems, several techniques have been devised. The following is a brief review of the methods used to generate human Mabs, and an overview of some of the uses of these reagents in clinical situations, with an emphasis on autoimmune and allergic disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Kohler, G. and Milstein, C. 1975. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256:495–497.

    Article  CAS  PubMed  Google Scholar 

  2. Kunkel, H.G., Slater, R.J. and Good, R.A. 1951. Relation between certain myeloma proteins and normal gamma globulin. Proc Soc Exp Biol Med 76:190–193.

    Article  CAS  PubMed  Google Scholar 

  3. Edelman, G.M. and Poulik, M.D. 1961. Studies on the structural units of the gamma globulins. J Exp Med 113:861–866.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Fleischman, J.B., Pain, R.H., and Porter, R.R. 1962. Reduction of the γ-globulins. Arch Biochem Biophys Suppl 1:174–178.

    CAS  Google Scholar 

  5. Kunkel, H.G., Mannik, M., and Williams, R.C. 1963. Individual antigenic specificity of isolated antibodies. Science (Wash. D.C.) 140:1218–1219.

    Article  CAS  Google Scholar 

  6. Yelton, D.E. and Scharff, M. 1981. Monoclonal antibodies: a powerful tool in biology and medicine. Ann Rev Biochem 50:657–680.

    Article  CAS  PubMed  Google Scholar 

  7. Kozbor, D. and Roder, J.C. 1983. The production of monoclonal antibodies from human lymphocytes. Immunology Today 4:72–79.

    Article  CAS  PubMed  Google Scholar 

  8. Cole, S.P., Campling, B.G., Atlaw, T., Kozbor, D., and Roder, J.C. 1984. Human monoclonal antibodies. Mol Cell Biochem 62:109–120.

    Article  CAS  PubMed  Google Scholar 

  9. Dorfman, N.A. 1985. The optimal technological approach to the development of human hybridomas. J Biol Response Mod 4:213–239.

    CAS  PubMed  Google Scholar 

  10. Miller, G. 1980. Biology of Epstein-Barr virus, p. 715–730. In: Viral Oncology. G. Klein (ed.), Raven Press, New York.

    Google Scholar 

  11. Fingeroth, J.D., Weis, J.J., Tedder, T.F., Strominger, P.A., Bird, P.A., and Fearon, D.T. 1984. Epstein-Barr virus receptor of human B lymphocytes is the C3d receptor CR2. Proc Natl Acad Sci USA 81:4510–4514.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Matsuo, T., Heller, M., Petti, L., O'Shiro, E., and Kieff, E. 1984. Persistence of the entire Epstein-Barr virus genome integrated into human lymphocyte DNA. Science 226:1322–1324.

    Article  CAS  PubMed  Google Scholar 

  13. Yates, J.L., Warren, N., and Sugden, B. 1985. Stable replication of plasmids derived from Epstein-Barr virus in various mammalian cells. Nature 313:812–815.

    Article  CAS  PubMed  Google Scholar 

  14. Brown, N.A. and Miller, G. 1982. Immunoglobulin expression by human B lymphocytes clonally transformed by Epstein-Barr virus. J Immunol 128:24–29.

    CAS  PubMed  Google Scholar 

  15. Stein, L.D., Ledgley, C.J., and Sigal, N.H. 1983. Patterns of isotype commitment in human B cells: limiting dilution analysis of Epstein-Barr virus-infected cells. J Immunol 130:1640–1645.

    CAS  PubMed  Google Scholar 

  16. Steinitz, M., Klein, G., Koskimies, S., and Makela, O. 1977. Polyclonal Ig production after Epstein-Barr virus infection of human lymphocytes in vitro. Nature 267:52–54.

    Article  Google Scholar 

  17. Kozbor, D., Steinitz, M., Klein, G., Koskimies, S., and Makela, O. 1979. Establishment of anti-TNP antibody-producing human lymphoid lines by preselection for hapten binding followed by EBV transformation. Scand J Immunol 10:187–194.

    Article  CAS  PubMed  Google Scholar 

  18. Boylston, A.W., Gardner, B., Anderson, R.L., and Hughes-Jones, N.C. 1980. Production of human IgM anti-D in tissue culture by EB-virus-transformed lymphocytes. Scand J Immunol 12:355–358.

    Article  CAS  PubMed  Google Scholar 

  19. Kozbor, D. and Roder, J.C. 1981. Requirements for the establishment of high-titered human monoclonal antibodies against tetanus toxoid using the Epstein-Barr virus technique. J Immunol 127:1275–1280.

    CAS  PubMed  Google Scholar 

  20. Steinitz, M., and Tamir, S. 1982. Human monoclonal autoimmune antibody produced in vitro: rheumatoid factor generated by Epstein-Barr virus-transformed cell line. Eur J Immunol 12:126–133.

    Article  CAS  PubMed  Google Scholar 

  21. Zurawski, V.R., Jr., Haber, E., and Black, P.M. 1978. Production of antibody to tetanus toxoid by continuous human lymphoblastoid cell lines. Science 199:1439–1441.

    Article  CAS  PubMed  Google Scholar 

  22. Yoshie, O., and Ono, Y. 1980. Anti-phosphorykholine antibody producing cells in human lymphoblastoid cell lines established by transformation with Epstein-Barr virus. Cell Immunol 56:305–315.

    Article  CAS  PubMed  Google Scholar 

  23. Stein, L.D., and Sigal, N.H. 1983. Limiting dilution analysis of Epstein-Barr virus-induced immunoglobulin production. Cell Immunol 79:309–319.

    Article  CAS  PubMed  Google Scholar 

  24. Steinitz, M., Seppala, F., Eichmann, K., and Klein, G. 1979. Establishment of a human lymphoblastoid cell line with specific antibody production against group A streptococcal carbohydrate. Immunobiology 156:41–47.

    CAS  PubMed  Google Scholar 

  25. Steinitz, M., Isak, G., Cohen, S., Ehrenfeld, M., and Flechner, I. 1980. Continuous production of monoclonal rheumatoid factor by EBV-transformed lymphocytes. Nature 287:443–445.

    Article  CAS  PubMed  Google Scholar 

  26. Rosen, A., Persson, K., and Klein, G. 1983. Human monoclonal antibodies to a genus-specific chlamydial antigen, produced by EBV-transformed B cells. J Immunol 130:2899–2902.

    CAS  PubMed  Google Scholar 

  27. Lundgren, K., Wahlgren, M., Troye-Blomberg, M., Berzins, K., Perlmann, H., and Perlmann, P. 1984. Monoclonal anti-parasite and anti-RBC antibodies produced by stable EBV-transformed B cell lines from malaria patients. J Immunol 131:2000–2003.

    Google Scholar 

  28. Olsson, L. and Kaplan, H.S. 1980. Human-human hybridomas producing monoclonal antibodies of predefined antigenic specificity. Proc Natl Acad Sci USA 77:5429–5433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Croce, C.M., Linnenback, A., Hall, W., Steplewski, Z., and Ko-prowski, H. 1980. Production of human hybridomas secreting antibody to measles virus. Nature 288:488–490.

    Article  CAS  PubMed  Google Scholar 

  30. Littman, B.H., Muchmore, A.V., Steinberg, A.D., and Greene, W.C. 1983. Monoclonal lupus autoantibody secretion by human-human hybridomas. Selection of hybrids by conventional and novel techniques. J Clin Invest 72:1987–1994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Szybalski, W., Szybalski, E.H., and Ragni, G. 1962. Genetic studies with human cell lines. Natl Cancer Inst Monogr 7:75–77.

    Google Scholar 

  32. Bischoff, R., Eisert, R.M., Schedel, I., Vienken, J., and Zimmerman, U. 1982. Human hybridoma cells produced by electro-fusion. FEBS Lett 4:64–68.

    Article  Google Scholar 

  33. Lo, M.M.S., Tsong, T.Y., Conrad, M.K., Strittmatter, S.M., Hester, L.D., and Snyder, S.H. 1984. Monoclonal antibody production by receptor-mediated electrically induced cell fusion. Nature 310:792–794.

    Article  CAS  PubMed  Google Scholar 

  34. Chiorazzi, N., Wasserman, R., and Kunkel, H.G. 1982. Use of Epstein-Barr virus transformed B cell lines for the generation of immunoglobulin-producing human B cell hybridomas. J Exp Med 156:930–935.

    Article  CAS  PubMed  Google Scholar 

  35. Kozbor, D., Dexter, D., and Roder, J.C. 1983. A comparative analysis of the phenotypic characteristics of available fusion partners for the contruction of human hybridomas. Hybridoma 2:7–16.

    Article  CAS  PubMed  Google Scholar 

  36. Edwards, P.A., Smith, C.M., Neville, A.M., and O'Hare, M.J. 1982. A human-human hybridoma system based on a fast-growing mutant of the ARH-77 plasma cell leukemia derived line. Eur J Immunol 12:641–648.

    Article  CAS  PubMed  Google Scholar 

  37. Heitzmann, J.G., and Cohn, M. 1983. The WI-L2-729-HF2 human hybridoma system. Stable hybrids at high frequency. Mol Biol Med 1:235–243, 1983.

    CAS  PubMed  Google Scholar 

  38. Glassy, M.C., Handley, H.H., Hagiwara, H., and Royston, I. 1983. UC 729-6, a human lymphoblastoid B-cell line useful for generating antibody-secreting human-human hybridomas. Proc Natl Acad Sci USA 80:6327–6331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Larrick, J.W., Truitt, K.E., Raubitschek, A.A., Senyk, G., and Wang, J.C. 1983. Characterization of human hybridomas secreting antibody to tetanus toxoid. Proc Natl Acad Sci USA 80:6376–6380.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Butler, J.L., Lane, H.C., and Fauci, A.S. 1983. Delineation of optimal conditions for producing mouse-human heterohybridomas from human peripheral blood B cells of immunized subjects. J Immunol 130:165–168.

    CAS  PubMed  Google Scholar 

  41. Sikora, K., Krikorian, J., and Levy, R. 1979. Monoclonal immunoglobulin rescue from a patient with chronic lymphocytic leukemia and autoimmune hemolytic anemia. Blood 54:513–518.

    Article  CAS  PubMed  Google Scholar 

  42. Lane, H.C., Shelhamer, J.H., Mostowski, H.S., and Fauci, A.S. 1982. Human monoclonal anti-KLH antibody-secreting hybridoma produced from peripheral blood B lymphocytes of a KLH-immune individual. J Exp Med 155:333–339.

    Article  CAS  PubMed  Google Scholar 

  43. Cote, R.J., Morrissey, D.M., Houghton, A.N., Beattie, E.J., Jr., Oettgen, H.R., and Old, L.J. Generation of human monoclonal antibodies reactive with cellular antigens. Proc Natl Acad Sci USA 80:2026–2030.

    Article  CAS  Google Scholar 

  44. Teng, N.N.H., Lam, K.S., Calvo-Riera, F., and Kaplan, H.S. 1983. Construction and testing of mouse-human heteromyelomas for human monoclonal antibody production. Proc Natl Acad Sci USA 80:7308–7312.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Posner, M.R., Schlossman, S.F., and Lazarus, H. 1983. Novel approach to construction of human ‘myeloma analogues’ for production of human monoclonal antibodies. Hybridoma 2:369–381.

    Article  CAS  PubMed  Google Scholar 

  46. Kozbor, D., Lagarde, A.E., and Roder, J.C. 1982. Human hybridomas constructed with antigen-specific Epstein-Barr virus-transformed cell lines. Proc Natl Acad Sci USA 79:6651–6655.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sikora, K., Alderson, T., Phillips, J., and Watson, J.V. 1982. Human hybridomas from malignant gliomas. Lancet 1:11–14.

    Article  CAS  PubMed  Google Scholar 

  48. Sikora, K. 1984. The characterization of gliomas using human monoclonal antibodies. Minireview on cancer research. Exp Cell Bio 52:189–195.

    CAS  Google Scholar 

  49. Teramoto, Y.A., Meriani, R., Wunderlich, D., and Schlom, J. 1982. The immunohistochernical reactivity of a human monoclonal antibody with tissue sections of human mammary tumors. Cancer 50:241–249.

    Article  CAS  PubMed  Google Scholar 

  50. Sikora, K., Alderson, T., Ellis, J., Phillips, J., and Watson, J. 1983. Human hybridomas from patients with malignant disease. Br J Cancer 47:135–145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Warenius, H.M., Taylor, J.W., Durack, B.E., and Cross, P.A. 1983. The production of human hybridomas from patients with malignant melanoma. Eur J Cancer Clin Oncol 19:347–355.

    Article  CAS  PubMed  Google Scholar 

  52. Hagiware, H., and Sato, G.H. 1983. Human X human hybridoma producing monoclonal antibody against autologous cervical carcinoma. Mol Biol Med 1:245–252.

    Google Scholar 

  53. Cole, S.P., Campling, B.G., Louwman, I.H., Kozbor, D., and Roder, J.C. 1984. A strategy for the production of human monoclonal antibodies reactive with lung tumor cell lines. Cancer Res 44:2750–2753.

    CAS  PubMed  Google Scholar 

  54. Hunter, K.W. Jr., Fischer, G.W., Hemming, V.G., Wilson, S.R., Harlzman, R.J., and Woody, J.N. 1982. Antibacterial activity of a human monoclonal antibody to haemophilus influenzae type B capsular polysaccharide. Lancet 2:798–799.

    Article  CAS  PubMed  Google Scholar 

  55. Schwaber, J.F., Posner, M.R., Schlossman, S.F., and Lazarus, H. 1984. Human-human hybrids secreting pneumococcal antibodies. Hum Immunol 9:137–143.

    Article  CAS  PubMed  Google Scholar 

  56. Crawford, D.H., Callard, R.E., Muggeridge, M.I., Mitchell, D.M., Zanders, E.D., and Beverley, P.C. 1983. Production of human monoclonal antibody to X31 influenza virus nucleoprotein. J Gen Virol 64:697–700.

    Article  PubMed  Google Scholar 

  57. Monjour, L., Desgranges, C., Alfred, C., Ploton, I., and Karabinis, A. 1983. Production of human monoclonal antibodies against asexual erythrocytic stages of Plasmodium falciparum. Lancet 1:1337–1338.

    Article  CAS  PubMed  Google Scholar 

  58. Emanual, D., Gold, J., Colacino, J., Lopez, C., and Hammerling, U. 1984. A human monoclonal antibody to cytomegaiovirus (CMV). J. Immunol 133:2202–2205.

    Google Scholar 

  59. Atlaw, T., Kozbor, D., and Roder, J.C. 1985. Human monoclonal antibodies against Mycobacterium leprae. Infect Immun 49:104–110.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Eisenbarth, G.S., Linnenbach, A., Jackson, R., Scearce, R., and Croce, C.M. 1982. Human hybridomas secreting anti-islet autoanti-bodies. Nature 300:264–267.

    Article  CAS  PubMed  Google Scholar 

  61. Shoenfeld, Y., Hsu-Lin, S.C., Gabriels, J.E., Silberstein, L.E., Furie, B.C., Furie, B., Stollar, B.D., and Schwartz, R.S. 1982. Production of autoantibodies by human-human hybridomas. J Clin Invest 70:205–208.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Littman, B.H., Muchmore, A.V., Steinberg, A.D., and Greene, W.C. 1983. Monoclonal autoantibody secretion by human-human hybridomas. J Clin Invest 72:1987–1994.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Chiorazzi, N., Bigler, R.D., Lahita, R.G., and Reeves, W.H. 1985. Antigen-binding characteristics of certain IgM anti-DNA human monoclonal antibodies. J Immunol (submitted).

  64. Cairns, E., Block, J., and Bell, D.A. 1984. Anti-DNA autoantibody-producing hybridomas of normal human lymphoid cell origin. J Clin Invest 74:880–887.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Massicotte, H., Rauch, J., Schoenfeld, Y., and Tannenbaum, H. 1984. Influence of fusion cell ratio and cell plating density on production of human-human hybridomas secreting anti-DNA auto-antibodies from patients with systemic lupus erythematosus. Hybridoma 3:215–222.

    Article  CAS  PubMed  Google Scholar 

  66. Raubitschek, A., Senyk, G., Larrick, J., Lizak, G., and Foung, S. 1985. Human monoclonal antibodies against group A red blood cells. Vox Sang 48:305–308.

    Article  CAS  PubMed  Google Scholar 

  67. Hulette, C.M., Effros, R.B., Dillard, L.C., and Walford, R.L. 1985. Production of a human monoclonal antibody to HLA by human-human hybridoma technology. A preliminary report. Am J Pathol 121:10–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Denis, K.A., Wall, R., and Saxon, A. 1983. Human-human B cell hybridomas from in vitro stimulated lymphocytes of patients with common variable immunodeficiency. J Immunol 131:2273–2278.

    CAS  PubMed  Google Scholar 

  69. Chiorazzi, N. 1986. An overview of cellular immune function in SLE. In: Systemic Lupus Erythematosus, R. G. Lahita (ed.) J. Wiley and Sons Publishers, NY.

    Google Scholar 

  70. Tan, E.M., Schur, P.H., Carr, R.I., and Kunkel, H.G. 1966. Deoxyribonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest 45:1732–1740.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Koffler, D., Carr, R., Agnello, V., Thoburn, R., and Kunkel, H.G. 1971. Systemic lupus erythematosus: Prototype of immune complex nephritis in man. J Exp Med 134:169s–179s.

    Article  CAS  PubMed  Google Scholar 

  72. Shoenfeld, Y., Rauch, J., Massicotte, H., Datta, S.K., Andre-Schwartz, J., Stollar, D., and Schwartz, R.S. 1983. Polyspetifitity of monoclonal lupus autoantibodies produced by human-human hybridomas. N Engl J Med 308:414–420.

    Article  CAS  PubMed  Google Scholar 

  73. Tan, E.M. 1982. Autoantibodies to nuclear antigens (ANA): Their immunobiology and medicine. Adv Immunol 33:167–240.

    Article  CAS  PubMed  Google Scholar 

  74. Andre-Schwartz, J., Datta, S.K., Shoenfeld, Y., Isenberg, D.A., Stollar, D., and Schwartz, R.S. 1984. Binding of cytoskeletal proteins by monoclonal anti-DNA lupus autoantibodies. Clin Immunol Immunopathol 31:261–271.

    Article  CAS  PubMed  Google Scholar 

  75. Senecal, J.L., Rothfield, N.F., and Oliver, J.M. 1982. Immunoglobulin M autoantibodies to vimentin intermediate filaments. J Clin Invest 69:716–721.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Alcover, A., Molano, J., Renart, J., Gil-Aguado, A., Nieto, A., and Avila, J. 1984. Antibodies to vimentin intermediate filaments in sera from patients with systemic lupus erythematosus. Arthritis Rheum 27:922–928.

    Article  CAS  PubMed  Google Scholar 

  77. Satoh, J., Prabhakar, B.S., Haspel, M.V., Ginsberg-Fellner, F., and Notkins, A.L. 1983. Human monoclonal autoantibodies that react with multiple endocrine organs. N Engl J Med 309:217–220.

    Article  CAS  PubMed  Google Scholar 

  78. Haspel, M.V., Onodera, T., Prabhakar, B.S., McClintock, P.R., Essani, K., Ray, U.R., Yagihashi, S., and Notkins, A.L. 1983. Multiple organ-reactive monoclonal antibodies. Nature 304:73–76.

    Article  CAS  PubMed  Google Scholar 

  79. Haspel, M.V., Onodera, T., Prabhakar, B.S., Horita, M., Suzuki, H., and Notkins, A.L. 1983. Virus-induced autoimmunity: Monoclonal antibodies that react with endocrine tissues. Science 220:304–306.

    Article  CAS  PubMed  Google Scholar 

  80. Eaton, R.B., Schneider, G., and Schur, P.H. 1983. Enzyme immu-noassay for antibodies to native DNA. Specificity and quality of antibodies. Arthritis Rheum 26:52–62.

    Article  CAS  PubMed  Google Scholar 

  81. Shoenfeld, Y., Isenberg, D.A., Rauch, J., Madaio, M.P., Stollar, B.D., and Schwartz, R.S. 1983. Idiotypic cross-reactions of monoclonal lupus autoantibodies. J Exp Med 158:718–730.

    Article  CAS  PubMed  Google Scholar 

  82. Isenberg, D.A., Shoenfeld, Y., Madaio, M.P., Rauch, J., Reichlin, M., Stollar, B.D., and Schwartz, R.S. 1984. Anti-DNA antibody idiotypes in systemic lupus erythematosus. Lancet 25:417–422.

    Article  Google Scholar 

  83. Atkinson, P.M., Lampman, G.W., Furie, B.C., Naparst, E.K., Schwartz, R.S., Stollar, B.D., and Furie, B. 1985. Homology of the NH2-terminal amino acid sequences of the heavy and light chains of human monoclonal lupus autoantibodies containing the dominant 16/6 idiotype. J Clin Invest 75:1138–1143.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Isenberg, D.A., Shoenfeld, Y., Walport, M., Mackworth-Young, C., Dudeney, C., Todd-Pokropek, A., Brill, S., Weinberger, A., and Pinkas, J. 1985. Detection of cross-reactive anti-DNA antibody idiotypes in the serum of systemic lupus erythematosus patients and of their relatives. Arthritis Rheum 28:999–1006.

    Article  CAS  PubMed  Google Scholar 

  85. Gearhardt, P., Johnson, N., Douglas, R., and Hood, L. 1981. IgG antibodies to phosphorylcholine exhibit more diversity than their IgM counterparts. Nature 291:29–34.

    Article  Google Scholar 

  86. Gorski, J., Rollini, P., and Mach, B. 1983. Somatic mutations of immunoglobulin variable genes are restricted to the rearranged V gene. Science 220:1179–1181.

    Article  CAS  PubMed  Google Scholar 

  87. Griffiths, G.M., Berek, C., Kaartinen, M., and Milstein, C. 1984. Somatic mutation and the maturation of the immune response to 2-phenyl oxazolone. Nature 312:271–275.

    Article  CAS  PubMed  Google Scholar 

  88. Berek, C., Griffiths, G.M., and Milstein, C. 1985. Molecular events during maturation of the immune response to oxazolone. Nature 316:412–418.

    Article  CAS  PubMed  Google Scholar 

  89. Liacopoulos, P., Amstutz, H., and Gille, F. 1971. Early antibody-forming cells of double specificity. Immunology 20:57–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Rosenstein, R.W., Musson, R.A., Armstrong, M.Y.K., Konigsberg, W.H., and Richards, F.F. 1972. Contact regions for dinitrophenyl and menadione haptens in an immunoglobulin binding more than one antigen. Proc. Natl Acad Sci USA 69:877–881.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Varga, J.M., Konigsberg, W.H., and Richards, F.F. 1973. Antibodies with multiple binding functions. Induction of single immunoglobulin species by structurally dissimilar haptens. Proc Natl Acad Sci USA 70:3269–3274.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. DeLuca, D., Decker, J., Miller, A., and Sercarz, E. 1974. Antigen binding to lymphoid cells from unimmunized mice: High frequency of β-galactosidase binding cells at optimal conditions. Cellular Immunol 10:1–18.

    Article  CAS  Google Scholar 

  93. Varga, J.M., Lande, S., and Richards, F.F. 1974. Immunoglobulins with multiple binding functions. II. The use of nylonpolyserine whisker discs in screening myeloma imfnunoglobulins for binding activity. J Immunol 112:1565–1570.

    CAS  PubMed  Google Scholar 

  94. DeLuca, D., Miller, A., and Sercarz, E. 1975. Antigen binding to lymphoid cells from unimmunized mice. II. High frequency of antigen-binding cells for several protein antigens by a morphologically distinct Ig-bearing population of T and B lymphocytes. Cellular Immunol 18:255–273.

    Article  CAS  Google Scholar 

  95. Liacopoulos, P., Couderc, J., and Bleux, C. 1976. Evidence for multipotentiality of antibody synthesizing cells. Ann Immunol (Inst Pasteur) 127C:519–530.

    Google Scholar 

  96. Cameron, D.J., and Erlanger, B.F. 1977. Evidence for multispecifi-city of antibody molecules. Nature 268:763–765.

    Article  CAS  PubMed  Google Scholar 

  97. Couderc, J., Birrien, J.L., Bleux, C., and Liacopoulos, P. 1977. Development of responsiveness and incidence of bispecific cells as revealed by in vitro assessment of the maturation of mouse bone marrow cells. Cellular Immunol 28:248–257.

    Article  CAS  Google Scholar 

  98. Rinnooy Kan, E.A., and Siskind, G.W. 1980. The transient appearance of degenerate antibody early in the course of the immune response. J Immunol 124:1758–1762.

    Google Scholar 

  99. Sperling, R., Francus, T., and Siskind, G.W. 1983. Degeneracy of antibody specificity. J Immunol 131:882–885.

    CAS  PubMed  Google Scholar 

  100. Guilbert, B., Dighiero, G., and Avrameas, S. 1982. Naturally occuring antibodies against nine common antigens in human sera. I. Detection, isolation, and characterization. J Immunol 128:2779–2787.

    CAS  PubMed  Google Scholar 

  101. Dighiero, G., Lymberi, P., Holmberg, D., Lundquist, I., Coutinho, A., and Avrameas, S. 1985. High frequency of natural autoantibodies in normal newborn mice. J Immunol 134:765–771.

    CAS  PubMed  Google Scholar 

  102. Dighiero, G., Guilbert, B., and Avrameas, S. 1982. Naturally occur-ing antibodies against nine common antigens in human sera. II. High incidence of monoclonal Ig exhibiting antibody activity against actin and tubulin and sharing antibody specificities with natural antibodies. J Immunol 128:2788–2792.

    CAS  PubMed  Google Scholar 

  103. Chiorazzi, N., and Reeves, W.H. 1985. Definition and partial characterization of a ribonucleoprotein autoantigen using a human monoclonal autoantibody. J Clin Invest (submitted).

  104. Holman, H.R. 1965. Partial purification and characterization of an extractable nuclear antigen which reacts with SLE sera. Ann NY Acad Sci 124:800–806.

    Article  CAS  PubMed  Google Scholar 

  105. Tan, E.M., and Kunkel, H.G. 1966. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol 96:464–471.

    CAS  PubMed  Google Scholar 

  106. Sharp, G.C., Irvin, W.S., LaRoque, R.L., Velez, C., Daly, V., Kaiser, A.D., and Holman, H.R. 1971. Association of autoantibodies to different nuclear antigens with clinical patterns of rheumatic disease and responsiveness to therapy. J Clin Invest 50:350–359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Sharp, G.C., Irvin, W.S., Tan, E.M., Gould, R.G., and Holman, H.R. 1972. Mixed connective tissue disease—an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Amer J Med 52:148–159.

    Article  CAS  PubMed  Google Scholar 

  108. Tamm, I. 1977. Definition of subclasses of nucleoplasmid RNA. Proc Natl Acad Sci USA 74:5011–5015.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Scheer, U., Hugle, B., Hazan, R., and Rose, K.M. 1984. Drug-induced dispersal of transcribed r RNA genes and transcriptional products: Immunolocalization and silver staining of different nucleolar components in rat cells treated with 5,6, dichloro-β-D-ribofuronosylbenzimidazole. J Cell Biol 99:672–679.

    Article  CAS  PubMed  Google Scholar 

  110. Homberg, J.C., Rizzetto, M., and Doniach, D. 1974. Ribosomal antibodies detected by immunofluorescence in systemic lupus erythematosus and other collagenoses. Clin Exp Immunol 17:617–628.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Miyachi, K., and Tan, E.M. 1979. Antibodies reacting with ribosomal ribonucleoprotein in connective tissue diseases. Arthritis Rheum 22:87–93.

    Article  CAS  PubMed  Google Scholar 

  112. Koffler, D., Miller, T.E., and Lahita, R.G. 1979. Studies on the specificity and clinical correlation of antiribosomal antibodies in systemic lupus erythematosus sera. Arthritis Rheum 22:463–470.

    Article  CAS  PubMed  Google Scholar 

  113. Meroni, P.L., De Bartolo, G., Barcellini, W., Riboldi, P.S., Basile, R., Betterle, C., and Zanussi, C. 1984. Anti-ribosomal ribonucleoprotein autoantibodies in systemic lupus erythematosus. J Clin Immunol 4:45–54.

    Article  CAS  PubMed  Google Scholar 

  114. Elkon, K.B., Parnassa, A.P., and Foster, C.L., 1985. Lupus autoantibodies target ribosomal P proteins. J Exp Med 162:459–471.

    Article  CAS  PubMed  Google Scholar 

  115. Francoeur, A.M., Peebles, C.L., Heckman, K.J., Lee, J.C., and Tan, E.M. 1985. Identification of antirivosomal protein autoantigens. J Immunol (in press).

  116. Nilsson, K., Bennich, H., Johansson, S.G.O., and Ponten, J. 1970. Established immunoglobulin producing myeloma (IgE) and lympho-blastoid (IgG) cell lines from an IgE myeloma patient. Clin Exp Immunol 7:477–489.

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Neuberger, M.S., Williams, G.T., Mitchell, E.B., Jouhal, S.S., Flanagan, J.G., and Rabbitts, T.H. 1985. A hapten-specific chimaeric IgE antibody with human physiological effector functions. Nature 314:268–270.

    Article  CAS  PubMed  Google Scholar 

  118. Ogawa, M., Nakahata, T., Leary, A.G., Sterk, A.R., Ishizaka, K., and Ishizaka, T. 1983. Suspension culture of human mast cells/basophils from umbilical cord blood mononuclear cells. Proc Natl Acad Sci USA 80:4494–4498.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Chiorazzi, N., Fisher, D.E., Shepherd, G., Sisking, G., and Ishizaka, T. 1985. Production of human IgE by B cell lines. J Exp Med (submitted).

  120. Schwartz, R.S. 1986. Autoantibodies and normal antibodies: Two sides of the same coin, Harvey Society Lecture. The Rockefeller University Press.

    Book  Google Scholar 

  121. Diamond, B., Scharff, M.D. 1984. Somatic mutation of the T15 heavy-chain gives rise to an antibody with autoantibody specificity. Proc Natl Acad Sci USA. 81:5841–5844.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Rockefeller University, 1230 York Avenue, New York, New York, 10021

    Nicholas Chiorazzi

Authors
  1. Nicholas Chiorazzi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chiorazzi, N. Human Monoclonal Antibodies as Probes to Study Autoimmune and Allergic Disorders. Nat Biotechnol 4, 210–218 (1986). https://doi.org/10.1038/nbt0386-210

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nbt0386-210

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing