Unique Features of the Antibody Problem

  • Thomas J. Kindt
  • J. Donald Capra


Information obtained in the serologic and structural studies described in the previous chapters revealed several striking features of antibodies and the genes that encode them. First of all, it became obvious that there was no known precedent for the immune system. No other biologic process requires the synthesis, on demand, of numerous large molecules with diverse binding properties. There have been attempts to equate olfaction or the general function of the nervous system to the immune system but these are not appropriate comparisons because these systems are not known to use large numbers of structurally distinct proteins in their functionings. Other multigene families such as those encoding ribosomal RNA or histones are required to carry out fixed functions rather than maintain the ability to generate diversity. Although there are a number of similarities between immunoglobulins and proteins encoded at the major histocompatibility complex, the analogy does not include a similar type of diversity.


Light Chain Heavy Chain Versus Region Major Histocompatibility Complex Antigen Myeloma Protein 
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References and Bibliography

  1. Baglioni, C., Cioli, D., Gorini, G., Ruffilli, A., and Alescio-Zonta, L., 1967, Studies on fragments of light chains of human immunoglobulins: Genetic and biochemical implications, Cold Spring Harbor Symp. Quant. Biol. 32: 147.CrossRefGoogle Scholar
  2. Beutler, E., Yeh, M., and Fairbanks, V. F., 1962, The normal human female as a mosaic of X chromosome activity: Studies using the gene for G-6-PD deficiency as a marker, Proc. Natl. Acad. Sci. U.S.A. 48: 9.PubMedCrossRefGoogle Scholar
  3. Beadle, G. W., and Tatum, E. L., 1941, Genetic control of biochemical reactions in neurospora, Proc. Natl. Acad. Sci. U.S.A. 27: 499.PubMedCrossRefGoogle Scholar
  4. Capra, J. D., Wasserman, R. L., and Kehoe, J. M., 1973, Phylogenetically associated residues with the VHIII subgroup of several mammalian species: Evidence for a “Pauci-Gene” basis for antibody diversity, J. Exp. Med. 138: 410.PubMedCrossRefGoogle Scholar
  5. Catty, D., Humphrey, J. H., and Gell, P. G. H., 1969, The proportion of two blocus allotypic determinants in rabbit antisera raised against pneumococcal polysaccharide SSS-III antigen, Immunology 16: 409.PubMedGoogle Scholar
  6. Conley, C. L., and Charache, S., 1973, Inherited hemoglobinopathies, in: Medical Genetics ( V. A. McKusick and R. Claiborne, eds.), H. P. Publishing Company, Inc., p. 53.Google Scholar
  7. Dreyer, W. N., and Bennett, J. C., 1965, The molecular basis of antibody formation: A paradox, Proc. Natl. Acad. Sci. U.S.A. 54: 864.PubMedCrossRefGoogle Scholar
  8. Dubiski, S., 1969, Immunochemistry and genetics of a “new” allotypic specificity Ae14 of rabbit 7G immunoglobulins: Recombination in somatic cells, J. Immunol. 103: 120.PubMedGoogle Scholar
  9. Dubiski, S., 1972, Genetics and regulation of immunoglobulin allotypes, Med. Clin. North Am. 56: 557.PubMedGoogle Scholar
  10. Eichmann, K., and Berek, C., 1973, Mendelian segregation of a mouse antibody idiotype, Eur. J. Immunol. 3: 599.PubMedCrossRefGoogle Scholar
  11. Eichmann, K., and Kindt, T. J., 1971, The inheritance of individual antigenic specificities of rabbit antibodies to streptococcal carbohydrates, J. Exp. Med. 134: 532.PubMedCrossRefGoogle Scholar
  12. Feinstein, A., 1963, Character and allotypy of an immune globulin in rabbit colostrum, Nature 199: 1197.PubMedCrossRefGoogle Scholar
  13. Fleischman, J. B., 1967, Synthesis of the rabbit gamma G heavy chain, Cold Spring Harbor Symp. Quant. Biol. 32: 233.CrossRefGoogle Scholar
  14. Foshay, M. C., Zimmerman, S. E., Spencer, L. K., Haurowitz, F., and Knight, K., 1976, Perferential expression of anti-azobenzenearsonate antibodies of heterozygous at a3 rabbits in the al allotype, J. Immunol. 116: 1010.PubMedGoogle Scholar
  15. Fu, S. M., Winchester, R. J., and Kunkel, H. G., 1975, Similar idiotypic specificity for the membrane IgD and IgM of human B lymphocytes, J. Immunol. 114: 250.PubMedGoogle Scholar
  16. Garrod, A. E., 1923, Inborn Errors of Metabolism, 2nd Ed., Oxford University Press, London.Google Scholar
  17. Harboe, M., Osterland, C. K., Mannik, M., and Kunkel, H. G., 1962, Genetic characters of human γ-globulins and myeloma proteins, J. Exp. Med. 116: 719.PubMedCrossRefGoogle Scholar
  18. Hilschmann, N., and Craig, L. C., 1965, Amino acid sequence studies with Bence-Jones proteins, Proc. Natl. Acad. Sci. U.S.A. 53: 1403.PubMedCrossRefGoogle Scholar
  19. Hood, L., Grant, J. A., and Sox, H. C., 1970, On the structure of normal light chains from mammals and birds: Evolutionary and genetic implications, in: Developmental Aspects of Antibody Formation and Structure, Vol. 1, ( J. Sterzl and I. Riha eds.), Academia Publishing House of the Czechoslovak Acadamy of Science, Prague, p. 283.Google Scholar
  20. Hopper, J. E., and Nisonoff, A., 1971, Individual antigenic specificity of immunoglobulins, Adv. Immunol. 13: 57.CrossRefGoogle Scholar
  21. Jerne, N. K., and Nordin, A. A., 1963, Plaque formation in agar by single antibody- producing cells, Science 140: 405.CrossRefGoogle Scholar
  22. Kabat, E., Wu, T. T., and Bilofsky, H., 1979, Sequence of immunoglobulin chains, U. S. Dept. Health, Education and Welfare, PHS, NIH, p. 121.Google Scholar
  23. Kindt, T. J., Mandy, W. J., and Todd, C. W., 1970, Association of allotypic specificities of group a with allotypic specificities All and A12 in rabbit immunoglobulin, Biochemistry 9: 2028.PubMedCrossRefGoogle Scholar
  24. Kindt, T. J., and Todd, C. W., 1969, Heavy and light chain allotypic markers on rabbit homocytotropic antibody, J. Exp. Med. 130: 859.PubMedCrossRefGoogle Scholar
  25. Knight, K. L., Malek, T. R., and Hanly, W. C., 1974, Recombinant rabbit secretory immunoglobulin molecules: Alpha chains with maternal (paternal) variable-region allotypes and paternal (maternal) constant-region allotypes, Proc. Natl. Acad. Sci. U.S.A. 71: 1169.PubMedCrossRefGoogle Scholar
  26. Koshland, M. E., Davis, J. J., and Fujita, N. J., 1969, Evidence for multiple gene control of a single polypeptide chain: The heavy chain of rabbit immunoglobulin, Proc. Natl. Acad. Sci. U.S.A. 63: 1274.PubMedCrossRefGoogle Scholar
  27. Kuettner, M. G., Wang, A., and Nisonoff, A., 1972, Quantitative investigations of idiotypic antibodies. VI. Idiotypic specificity as a potential genetic marker for the variable regions of mouse immunoglobulin polypeptide chains, J. Exp. Med. 135: 579.PubMedCrossRefGoogle Scholar
  28. Kunkel, H. G., 1970, Experimental approaches to homogeneous antibody populations: Individual antigenic specificity, cross specificity and diversity of human antibodies, Fed. Proc. 29: 55.PubMedGoogle Scholar
  29. Lennox, E. S., Knopf, P. M., Munro, A. J., and Parkhouse, R. M. E., 1967, A search for biosynthetic subunits of light and heavy chains of immunoglobulins, Cold Spring Harbor Symp. Quant. Biol. 32: 249.CrossRefGoogle Scholar
  30. Lyon, M. F., 1961, Gene action in the X-chromosome of the mouse (mus musculus L.), Nature (London) 190: 372.CrossRefGoogle Scholar
  31. Mage, R. G., Young-Cooper, G. O., and Alexander, C., 1971, Genetic control of variable and constant regions of immunoglobulin heavy chains, Nature (New Biol.) 230: 63.Google Scholar
  32. Mandy, W. J., and Todd, C. W., 1968, Allotypy of rabbit immunoglobulin: An agglutinating specificity, Vox Sanguinis 14: 264.PubMedCrossRefGoogle Scholar
  33. Nathenson, S. G., Uehara, H., Ewenstein, B. M., Kindt, T. J., and Coligan, J. E., 1981, Primary structural analysis of the transplantation antigens of the murine H-2 major histocompatibility complex, Annu. Rev. Biochem. 50: 1025.PubMedCrossRefGoogle Scholar
  34. Ohno, S., Weiler, C., Poole, J., Christian, L., and Stenius, C., 1966, Autosomal polymorphism due to Pericentric inversions in the deer mouse (Peromyscus maniculatus) and some evidence of somatic segregation, Chromosoma (Berlin) 18: 177.CrossRefGoogle Scholar
  35. Oudin, J., and Michel, M., 1969, Idiotypy of rabbit antibodies. II. Comparison of idiotypy of various kinds of antibodies formed in the same rabbits against Salmonella typhi, J. Exp. Med. 130: 619.PubMedCrossRefGoogle Scholar
  36. Pernis, B., Chiappino, G., Kelus, A., and Gell, P. G. H., 1965, Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues, J. Exp. Med. 122: 853.PubMedCrossRefGoogle Scholar
  37. Putnam, F. W., Titani, K., Wikler, M., and Shinoda, T., 1967, Structure and evolution of kappa and lambda light chains, Cold Spring Harbor Symp. Quant. Biol. 32: 9.CrossRefGoogle Scholar
  38. Strominger, J. L., Orr, H. T., Parham, P., Ploegh, H. L., Mann, D. L., Bilofsky, H., Saroff, H. A., Wu, T. T., and Kabat, E. A., 1980, An evaluation of the significance of amino acid sequence homologies in human histocompatibility antigens (HLA-A and HLA- B) with immunoglobulins and other proteins, using relatively short sequences, Scand. J. Immunol. 11: 573.PubMedCrossRefGoogle Scholar
  39. Todd, C. W., 1963, Allotypy in rabbit 19S protein, Biochem. Biophys. Res. Commun. 11: 170.PubMedCrossRefGoogle Scholar
  40. Wabl, M. R., and Tenkhoff, M., 1982, Allelic exclusion of immunoglobulin expression is not caused by somatic segregation, Proc. Natl. Acad. Sci. U.S.A. 79: 606–607.PubMedCrossRefGoogle Scholar
  41. Wang, A.-C., Wang, I. Y. F., McCormick, J. N., and Fudenberg, H. H., 1969, The identity of light chains of monoclonal IgG and monoclonal IgM in one patient, Immunochemistry 6: 451.PubMedCrossRefGoogle Scholar
  42. Wang, A. C., Wang, I. Y. F., and Fudenberg, H. H., 1977, Immunoglobulin structure and genetics: Identity between variable regions of a μ and a γ2 chain, J. Biol. Chem. 252: 7192.PubMedGoogle Scholar
  43. Weigert, M., and Potter, M., 1977, Antibody variable-region genetics: Summary and abstract of the Homogeneous Immunoglobulin Workshop VII, Immunogenetics 4: 401.CrossRefGoogle Scholar
  44. Weiler, E., 1965, Differential activity of allelic γ-globulin genes in antibody-producing cells, Proc. Natl. Acad. Sci. U.S.A. 54: 1765.PubMedCrossRefGoogle Scholar
  45. Wilkinson, J. M., 1969, Variation in the N-terminal sequence of heavy chains of immu-noglobulin G from rabbits of different allotype, Biochem. J. 112: 173.PubMedGoogle Scholar
  46. Wu, T. T., and Kabat, E. A., 1970, The analysis of the sequence of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity, J. Exp. Med. 132: 211.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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