The Molecular Biologists Attack the Problem

  • Thomas J. Kindt
  • J. Donald Capra


Studies on the nucleic acids involved in immunoglobulin synthesis had been underway for over a decade when the major breakthroughs came with the application of recombinant DNA technology to the antibody problem in the late 1970s. The essential groundwork for these break-throughs had been laid by the discovery of the mouse myelomas by Potter and their adaptation to tissue culture. The new wave of discovery would be further based on the early work by Askonas, Williamson, Stavitsky, Scharff, Milstein, Mach, and others who isolated mRNA from these tumors and developed techniques for its purification and enrichment as well as assays for the synthesis in vitro of immunoglobulin polypeptide chains. The first decade of work on nucleic acids was not particularly fruitful because the powerful technologies that emerged in the mid 1970s and were immediately applied to the antibody problem had not yet been developed.


Light Chain Heavy Chain Gene Segment Molecular Biologist Immunoglobulin Gene 
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References and Bibliography

  1. Askonas, B. A., and Williamson, A. R., 1967, Biosynthesis and assembly of immuno-globulin G, Cold Spring Harbor Symp. Quant. Biol. 32: 223.CrossRefGoogle Scholar
  2. Bentley, D. L., and Rabbitts, T. H., 1983, Evolution of immunoglobulin V genes: Evidence indicating that recently duplicated human VK sequences have diverged by gene conversion, Cell 32: 181.PubMedCrossRefGoogle Scholar
  3. Blomberg, B., and Tonegawa, S., 1982, DNA sequences of the joining regions of mouse k light chain immunoglobulin genes, Proc. Natl. Acad. Sci. U.S.A. 79: 530.PubMedCrossRefGoogle Scholar
  4. Bothwell, A. L. M., Paskind, M., Reth, M., Imanishi-Kari, T., Rajewsky, K., and Baltimore, D., 1981, Heavy chain variable region contribution to the NPb family of antibodies: Somatic mutations evident in a 72a variable region, Cell 24: 625.PubMedCrossRefGoogle Scholar
  5. Brack, C, and Tonegawa, S., 1977, Variable and constant parts of the immunoglobulin light chain gene of a mouse myeloma cell are 1250 nontranslated bases apart, Proc. Natl. Acad. Sci. U.S.A. 74: 5652.PubMedCrossRefGoogle Scholar
  6. Delovitch, T. L., and Baglioni, C., 1973, Estimation of light-chain gene reiteration of mouse immunoglobulin by DNA-RNA hybridization, Proc. Natl. Acad. Sci. U.S.A. 70: 173.PubMedCrossRefGoogle Scholar
  7. Early, P., Huang, H., Davis, J., Calame, K., and Hood, L., 1980, An immunoglobulin heavy chain variable region gene is generated from three segments of DNA:VH, D and JH, Cell 19: 981.PubMedCrossRefGoogle Scholar
  8. Early, P., Rogers, J., Davis, M., Calame, K., Bond, M., Wall, R., and Hood, L., 1980, Two mRNAs can be produced from a single immunoglobulin gene by alternative RNA processing pathways, Cell 20: 313.PubMedCrossRefGoogle Scholar
  9. Emorine, L., Dreher, K., Kindt, T. J., and Max, E. E., 1983, Rabbit immunoglobulin kappa genes: Structure of a germline b4 allotype J-C locus and evidence for several b4-related sequences in the rabbit genome, Proc. Natl. Acad. Sci. USA 80: 5709.PubMedCrossRefGoogle Scholar
  10. Farace, M.-G., Aellen, M.-F., Briand, P.-A., Faust, C. H., Vassali, P., and Mach, B., 1976, No detectable reiteration of genes coding for mouse MOPC41 immunoglobulin light- chain mRNA, Proc. Natl. Acad. Sci. U.S.A. 73: 727.PubMedCrossRefGoogle Scholar
  11. Gearhart, P. J., 1982, Generation of immunoglobulin variable gene diversity, Immunol. Today 3: 107.CrossRefGoogle Scholar
  12. Givol, D., Zakut, R., Effron, K., Rechavi, G., Ram, D., and Cohen, J. B., 1981, Diversity of germ-line immunoglobulin VH genes, Nature (London) 292: 426.CrossRefGoogle Scholar
  13. Hieter, P. A., Korsmeyer, S. J., Waldmann, T. A., and Leder, P., 1981, Human immunoglobulin light-chain genes are deleted or rearranged in γ-producing B cells, Nature (London) 290: 368.CrossRefGoogle Scholar
  14. Honjo, T., 1982, The molecular mechanism of immunoglobulin class switch, Immunol. Today 3: 214.CrossRefGoogle Scholar
  15. Knapp, M. R., Liu, C.-P., Newell, N., Ward, R. B., Tucker, P. W., Strober, S., and Blattner, F., 1982, Simultaneous expression of immunoglobulin μ and 8 heavy chains by a cloned B-cell lymphoma: A single copy of the VH gene is shared by two adjacent CH genes, Proc. Natl. Acad. Sci. U.S.A. 79: 2996.PubMedCrossRefGoogle Scholar
  16. Korsmeyer, S. J., Arnold, A., Bakhshi, A., Ravetch, J. V., Siebenlist, U., Hieter, P. A., Sharrow, S. O., LeBien, T. W., Kersey, J. H., Poplack, D. G., Leder, P., and Waldmann, T. A., 1983, Immunoglobulin gene rearrangement and cell surface antigen expression in acute lymphocytic leukemias of T cell and B cell precursor origins, J. Clin. Invest. 71: 301.PubMedCrossRefGoogle Scholar
  17. Kurosawa, Y., and Tonegawa, S., 1982, Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments, J. Exp. Med. 155: 201.PubMedCrossRefGoogle Scholar
  18. Leder, P., 1982, The genetics of antibody diversity, Sci. Am. 246: 108.CrossRefGoogle Scholar
  19. Leder, P., Honjo, T., Swan, D., Packman, S., and Norman, B., 1974, The organization and diversity of immunoglobulin genes, Proc. Natl. Acad. Sci. U.S.A. 71: 5109.PubMedCrossRefGoogle Scholar
  20. Leder, P., Max, E. E., and Seidman, J. G., 1980, The organization of immunoglobulin genes and the origin of their diversity, in: Fourth International Congress of Immunology, Immunology 80, Volume 2, ( M. Fougereau and J. Daussets, eds.), Academic Press, London, pp. 34–50.Google Scholar
  21. Max, E. E., Seidman, J. G., and Leder, P., 1979, The sequences of five potential recombination sites encoded close to an immunoglobulin kappa constant region gene, Proc. Natl. Acad. Sci. U.S.A. 76: 3450.PubMedCrossRefGoogle Scholar
  22. Max, E. E., Seidman, J. G., Miller, H., and Leder, P., 1980, Variation in the crossover point of kappa immunoglobulin gene V-J recombination: Evidence from a cryptic gene, Cell 21: 793.PubMedCrossRefGoogle Scholar
  23. Maxam, A. M., and Gilbert, W., 1980, Sequencing end-labeled DNA with base-specific chemical cleavages, Meth. Enzymol. 65: 499.PubMedCrossRefGoogle Scholar
  24. McBride, O. W., Hieter, P. A., Hollis, G. F., Swan, D., Otey, M. C., and Leder, P., 1982, Chromosomal location of human kappa and lambda immunoglobulin light chain constant region genes, J. Exp. Med. 155: 1480.PubMedCrossRefGoogle Scholar
  25. Potter, M., and Lieberman, R., 1967, Genetics of immunoglobulins in mice, Adv. Immunol. 7: 92.Google Scholar
  26. Premkumar, E., Shoyab, M., and Williamson, A. R., 1974, Germline basis for antibody diversity: Immunoglobulin VH and CH-gene frequencies measured by DNA-RNA hybridization, Proc. Natl. Acad. Sci. U.S.A. 71: 99.PubMedCrossRefGoogle Scholar
  27. Rabbitts, T., and Milstein, C., 1975, Mouse immunoglobulin genes: Studies on the re-iteration frequency of light-chain genes by hybridization procedures, Eur. J. Biochem. 52: 125.PubMedCrossRefGoogle Scholar
  28. Rechavi, G., Bienz, B., Ram, D., Ben-Neriah, Y., Cohen, J. B., Zakut, R., and Givol, D., 1982, Organization and evolution of immunoglobulin VH gene subgroup, Proc. Natl. Acad. Sci. U.S.A. 79: 4405.PubMedCrossRefGoogle Scholar
  29. Reth, M., Imanishi-Kari, T., and Rajewsky, K., 1979, Analysis of the repertoire of anti (4- hydroxy-3-nitro-phenyl) acetyl (NP) antibodies in C57BL/6 mice by cell fusion, Eur. J. Immunol. 9: 1004.PubMedCrossRefGoogle Scholar
  30. Rogers, J., Early, P., Carter, C., Calame, K., Bond, M., Hood, L., and Wall, R., 1980, Two mRNAs with different 3’ ends encode membrane-bound and secreted forms of immunoglobulin chain, Cell 20: 303.PubMedCrossRefGoogle Scholar
  31. Sanger, F., Nicklen, S., and Coulson, A. R., 1977, DNA sequencing with chain-terminating inhibitors, Proc. Natl. Acad. Sci. U.S.A. 74: 5463.PubMedCrossRefGoogle Scholar
  32. Seidman, J. G., Leder, A., Edgell, M. H., Polsky, F., Tilghman, S. M., Tiemeier, D. C., and Leder, P., 1978, Multiple related immunoglobulin variable-region genes identified by cloning and sequence analysis, Proc. Natl. Acad. Sci. U.S.A. 75: 3881.PubMedCrossRefGoogle Scholar
  33. Seising, E., Miller, J., Wilson, R., and Storb, U., 1982, Evolution of mouse immunoglobulin X genes, Proc. Natl. Acad. Sci. U.S.A. 79: 4681.CrossRefGoogle Scholar
  34. Sheppard, H. W., and Gutman, G. A., 1982, Rat kappa-chain J-segment genes: Two recent gene duplications separate rat and mouse, Cell 29: 121.PubMedCrossRefGoogle Scholar
  35. Siebenlist, U., Ravetch, J. V., Korsmeyer, S., Waldmann, T., and Leder, P., 1981, Human immunoglobulin D segments encoded in tandem multigenic families, Nature 294: 631.PubMedCrossRefGoogle Scholar
  36. Shimizu, A., Takahashi, N., Yaoita, Y., and Honjo, T., 1982, Organization of the constant- region gene family of the mouse immunoglobulin heavy chain, Cell 28: 499.PubMedCrossRefGoogle Scholar
  37. Smith, G. P., 1977, The significance of hybridization kinetic experiements for theories of antibody diversity, Cold Spring Harbor Symp. Quant. Biol. 41: 863.Google Scholar
  38. Southern, E. M., 1975, Detection of specific DNA sequences among DNA fragments separated by gel electrophoresis, J. Mol. Biol. 98: 503.PubMedCrossRefGoogle Scholar
  39. Storb, U., 1974, Evidence for multiple immunoglobulin genes, Biochem. Biophy. Res. Comm. 57: 31.CrossRefGoogle Scholar
  40. Tonegawa, S., Bernardini, A., Weimann, B. J., and Steinberg, C., 1974, Reiteration frequency of antibody genes. Studies with K chain mRNA. F.E.B.S. Lett. 40: 92.Google Scholar
  41. Tonegawa, S., Hozumi, N., Matthyssens, G., and Schuller, R., 1976, Somatic changes in the content and context of immunoglobulin genes, Cold Spring Harbor Symp. Quant. Biol. 41: 877.CrossRefGoogle Scholar
  42. Tonegawa, S., Maxam, A. M., Tizard, R., Bernard, O., and Gilbert, W., 1978, Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain, Proc. Natl. Acad. Sci. U.S.A. 75: 1485.PubMedCrossRefGoogle Scholar
  43. Valbuena, O., Marcu, K. B., Weigert, M., and Perry, R. P., 1978, Multiplicity of germline genes specifying a group of related mouse K chains with implications for the generation of immunoglobulin diversity, Nature 276: 780.PubMedCrossRefGoogle Scholar
  44. Van Ness, B. G., Coleclough, C., Perry, R. P., and Weigert, M., 1982, DNA between variable and joining gene segments of immunoglobulin K light chain is frequently retained in cells that rearrange the K locus, Proc. Natl. Acad. Sci. U.S.A. 79: 262.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Thomas J. Kindt
    • 1
  • J. Donald Capra
    • 2
  1. 1.National Institute of Allergy and Infectious DiseasesNational Institutes of HealthBethesdaUSA
  2. 2.University of Texas Health Science CenterDallasUSA

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