Advertisement

Normal and altered phenotypic expression of immunoglobulin genes

  • Rose G. Mage
Part of the Faseb Monographs book series (FASEBM, volume 3)

Abstract

Genetically controlled intraspecific differences between immunoglobulins (allotypes) provide valuable markers for the study of the quantitative expression of allelic and nonallelic alternative forms of immunoglobulins (Igs) during the normal development of rabbits. Heterozygous rabbits are mosaics of cells expressing different Ig-genes since fully differentiated productive cells generally secrete only one of alternative forms of Ig. The proportions of cells that differentiate to produce allelic forms of immunoglobulins during normal development depend on the particular heterozygous genotype. The normal proportions of some markers can be drastically altered if the differentiation of lymphoid cells in the young rabbit occurs in a milieu of antibody specific for one form (allotype suppression). An initiating step in the establishment of persistent allotype suppression is probably the interaction of antiallotype antibody with allotype-bearing receptors on lymphoid cell surfaces, but the mechanism for the maintenance of a state of chronic suppression may well be more complex. Allotype suppression can be viewed as one example of numerous immunological phenomena that reflect specific and finely tuned regulatory mechanisms governing the differentiation and clonal expansion of lymphoid cells destined to secrete immunoglobulins.—Mage, R. G. Normal and altered phenotypic expression of immunoglobulin genes. Federation Proc. 34: 40–46, 1975.

Keywords

Heavy Chain Constant Region Immunoglobulin Gene Allelic Form Young Rabbit 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Appella, E., A. Chersi, R. G. Mage and S. Dubiski: Structural basis of the A14 and A15 allotypic specificities in rabbit immunoglobulin G. Proc. Natl. Acad. Sci. U.S. 68: 1341, 1971.CrossRefGoogle Scholar
  2. 2.
    Appella, E., and J. K. Inman: The primary structure of rabbit and mouse immunoglobulin light chains: structural correlates of allotypy. In: Topics in Molecular Immunology, edited by R. A. Reisfeld and W. J. Mandy. New York: Plenum, 1973.Google Scholar
  3. 3.
    Catty, D., L. Chambers and J. A. Lowe: Humoral aspects of immunoglobulin allotype suppression in the rabbit. II. Effect of b locus suppression on immunoglobulin receptor-bearing lymphocytes. Immunology 26: 331, 1974.PubMedGoogle Scholar
  4. 4.
    Cebra, J. J., J. E. Colberg and S. Dray: Rabbit lymphoid cells differentiated with respect to a-, y-and ix-heavy polypeptide chains and to allotypic markers Aal and Aa2. J. Exptl. Med. 123: 547, 1966.CrossRefGoogle Scholar
  5. 5.
    Cinader, B., S. W. Koh and P. Kuksin: Allotype levels in normal and allotype suppressed mice after allogeneic stimulation. Cell. Immunol. 11: 170, 1974.PubMedCrossRefGoogle Scholar
  6. 6.
    David, G. S., and C. W. Todd: Suppression of heavy and light chain allotypic expression in homozygous rabbits through embryo transfer. Proc. Natl. Acad. Sci. U.S. 62: 860, 1969.CrossRefGoogle Scholar
  7. 7.
    Dray, S.: Effect of maternal isoantibodies on the quantitative expression of two allelic genes controlling y-globulin allotypic specificities. Nature 195: 677, 1962.PubMedCrossRefGoogle Scholar
  8. 8.
    Dray, S., B. S. Kim and A. Gilmansachs: Allogroups of rabbit Ig heavy chains. Ann. Immunol. Paris 125c: 41, 1974.Google Scholar
  9. 9.
    Dubiski, S.: Suppression of the synthesis of allotypically defined immunoglobulins and compensation by another subclass of immunoglobulin. Nature 214: 1365, 1967.PubMedCrossRefGoogle Scholar
  10. 10.
    Gally, J. A., and G. M. Edelman: The genetic control of immunoglobulin synthesis. Ann. Rev. Genetics 6: 1, 1972.CrossRefGoogle Scholar
  11. 11.
    Gilman-Sachs, A., R. G. Mage, G. O. Young, C. Alexander and S. Dray: Identification and genetic control of two rabbit immunoglobulin allotypes at a second light chain locus, the c locus. J. Immunol. 103: 1159, 1969.PubMedGoogle Scholar
  12. 12.
    Harrison, M. R., G. J. Elfenbein and R. G. Mage: Defective activation of b5 bearing lymphocytes in rabbits recovering from b5 allotype suppression. Cell. Immunology11: 231, 1974.CrossRefGoogle Scholar
  13. 13.
    Harrison, M. R., P. P. Jones and R. G. Mage. Endogenous synthesis of membrane b5 by lymphocytes from rabbits recovering from b5 allotype suppression. J. Immunol. 111: 1595, 1973.PubMedGoogle Scholar
  14. 14.
    Harrison, M. R., and R. G. Mage: Allotype suppression in the rabbit. I. The ontogeny of cells bearing immunoglobulin of paternal allotype and the fate of these cells after treatment with antiallotype antisera. J. Exptl. Med. 138: 764, 1973.CrossRefGoogle Scholar
  15. 15.
    Harrison, M. R., R. G. Mage and J. M. Davie: Deletion of b5 immunoglobulinbearing lymphocytes in allotype-suppressed rabbits. J. Exptl. Med. 137: 254, 1973.CrossRefGoogle Scholar
  16. 16.
    Herzenberg, L. A., E. L. Chan, M. M. Ravitch, R. J. Riblet and L. A. Herzenberg: Active suppression of immunoglobulin allotype synthesis. III. Identification of T cells as responsible for suppression by cells from spleen, thymus, lymph node, and bone marrow. J. Exptl. Med. 137: 1311, 1973.CrossRefGoogle Scholar
  17. 17.
    Inman, J. K., and R. A. Reisfeld: Differences in amino acid composition of papain Fd fragments from rabbit yGimmunoglobulins carrying different H chain allotypic specificities. Immunochemistry 5: 415, 1968.CrossRefGoogle Scholar
  18. 18.
    Jacobson, E. B.: In vitro studies of allo-type suppression in mice. European J. Immunol. 3: 619, 1973.CrossRefGoogle Scholar
  19. 19.
    Jerne, N. K.: Towards a network theory of the immune system. Ann. Immunol. Paris 125c: 373, 1974.Google Scholar
  20. 20.
    Kim, B. S., and S. Dray: Identification and genetic control of allotypic specificities on two variable region subgroups of rabbit immunoglobulin heavy chains. European J. Immunol. 2: 509, 1972.CrossRefGoogle Scholar
  21. 21.
    Kim, B. S., and S. Dray: Expression of the a, x, and y variable region genes of heavy chains among IgG, IgM, and IgA molecules of normal and a locus allotype-suppressed rabbits. J. Immunol. 111: 750, 1973.PubMedGoogle Scholar
  22. 22.
    Kindt, T. J.. and W. J. Mandy: Recombination of genes coding for constant and variable regions of immunoglobulin heavy chains. J. Immunol. 108: 1110, 1972.PubMedGoogle Scholar
  23. 23.
    Kindt, T. J., W. J. Mandy and C. W. Todd: Association of group a with allotypic specificities All and Al2 in rabbit immunoglobulin. Biochemistry 9: 2028, 1970.PubMedCrossRefGoogle Scholar
  24. 24.
    Klinman, N. R., and J. L. Press: Expression of specific clones during B-cell development. Federation Proc. 34: 47, 1975.Google Scholar
  25. 25.
    Koshland, M. E.: Location of specificity and allotypic amino acid residues in antibody Fd fragments. Cold Spring Harbor Symp. Quant. Biol. 32: 119, 1967.CrossRefGoogle Scholar
  26. 26.
    Lammert, J. M., W. C. Hanley, K. L. Knight, E. A. Lichter and S. Dray: Identification and characterization of additional rabbit IgA allotypes. Federation Proc. 33: 737, 1974.Google Scholar
  27. 27.
    Landucci Tosi, S., R. G. Mage and S. Dubiski: Distribution of allotypic specificities Al, A2, A14 and A15 among immunoglobulin G molecules. J. Immunol. 104: 641, 1970.Google Scholar
  28. 28.
    Landucci Tosi, S., and R. M. Tosi: Recombinant IgG molecules in rabbits doubly heterozygous for group a and group e allotypic specificities. Immunochemistry 10: 65, 1973.CrossRefGoogle Scholar
  29. 29.
    Linthicum, D. S., W. Mayr, K. Miyai and S. Sell: Endocytosis of lymphocyte surface immunoglobulin in the absence of cap formation demonstrated by ultrastructural labelling. Federation Proc. 32: 983, 1973.Google Scholar
  30. 30.
    Loor, F., L. Forni and B. Pernis: The dynamic state of the lymphocyte membrane. Factors affecting the distribution 41. and turnover of surface immunoglobulins. European J. Immunol. 2: 203, 1972.CrossRefGoogle Scholar
  31. 31.
    Lowe, J. A., L. M. Cross and D. Catty: Humoral and cellular aspects of immunoglobulin allotype suppression in the rabbit. I. Kinetics of neutralization of suppression. Immunology 25: 367, 1973.PubMedGoogle Scholar
  32. 32.
    Mage, R. G.: Quantitative studies on the regulation of expression of genes for immunoglobulin allotypes in heterozygous rabbits. Cold Spring Harbor Symp. Quant. Biol. 32: 203, 1967.CrossRefGoogle Scholar
  33. 33.
    Mage, R. G.: Altered quantitative expression of immunoglobulin allotypes in 44 rabbits. In: Current Topics in Microbiology and Immunology, vol. 63, edited by N. Jerne. Heidelberg: Springer-Verlag, 1974, p. 131.Google Scholar
  34. 34.
    Mage, R., R. Lieberman, M. Potter and W. D. Terry: Immunoglobulin allotypes. In: The Antigens, vol. 1, edited by M. Seal. New York: Academic, 1973, p. 229.Google Scholar
  35. 35.
    Mage, R. G., G. O. Young-Cooper and C. Alexander: Genetic control of variable and constant regions of immunoglobulin heavy chains. Nature New Biol. 230: 63, 1971.PubMedGoogle Scholar
  36. 36.
    Mage, R. G., G. O. Young and R. A. Reisfeld: The association of the c7 allotype of rabbits with some light polypeptide chains which lack b locus allo- 47. type./ Immunol. 101: 617, 1968.Google Scholar
  37. 37.
    Mole, L. E., S. S. Jackson, R. R. Porter and J. M. Wilkinson: Allotypically related sequences in the Fd fragment of rabbit immunoglobulin heavy chains. Biochem. J. 124: 301, 1971.PubMedGoogle Scholar
  38. 38.
    Oudin, J.: Reaction de precipitation specifique entre des serums d’animaux de meme espece. Compt. Rend. Acad. Sci. 242: 2489, 1956.Google Scholar
  39. 39.
    Oudin, J.: L’Allotypie de certains antigens proteidiques du serum. Compt. Rend. Acad. Sci. 242: 2606, 1956.Google Scholar
  40. 40.
    Oudin, J.: Allotypy of rabbit serum proteins. II. Relationships between various allotypes: their common antigenic specificity, their distribution in a sample population; genetic implications. J. Exptl. Med. 112: 125, 1960.CrossRefGoogle Scholar
  41. 41.
    Pernis, B., G. Chiappino, A. Kelus and P. Gell: Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues. J. Exptl. Med. 122: 853, 1965.CrossRefGoogle Scholar
  42. 42.
    Pernis, B., L. Forni, S. Dubski, A. S. Kelus, W. J. Mandy and C. W. Todd: Heavy chain variable and constant region allotypes in single rabbit plasma cells. Immunochemistry 10: 281, 1973.PubMedCrossRefGoogle Scholar
  43. 43.
    Prahl, J. W., W. J. Mandy and C. W. Todd: The molecular determinants of the All and Al2 allotypic specificities in rabbit immunoglobulin. Biochemistry 8: 4935, 1969.PubMedCrossRefGoogle Scholar
  44. 44.
    Sell, S.: Studies on rabbit lymphocytes in vitro. IX. The suppression of antiallotype-induced blast transformation in lymphocyte cultures from allotypically suppressed donors. J. Exptl. Med. 128: 341, 1968.CrossRefGoogle Scholar
  45. 45.
    Taylor, R. B., P. H. Duffus, M. C. Raff and S. Petris: Redistribution and pinocytosis of lymphocyte surface immunoglobulin molecules induced by antiimmunoglobulin antibody. Nature New Biol. 233: 225, 1971.PubMedCrossRefGoogle Scholar
  46. 46.
    Vice, J. L., A. Gilman-Sachs, W. L. Hunt and S. Dray: Allotype suppression in aia’ homozygous rabbits fostered in uteri of a2-immunized a’a’ homozygous mothers and injected at birth with anti-a2 antiserum. J. Immunol. 104: 550, 1970.PubMedGoogle Scholar
  47. 47.
    Vice, J. L., W. L. Hunt and S. Dray: Zygote transfer to facilitate altered expression of immunoglobulin light chain phenotypes in homozygous rabbits.Proc. Soc. Exptl. Biol. Med. 130: 730, 1969.Google Scholar
  48. 48.
    Vice, J. L., W. L. Hunt and S. Dray: Allotype suppression with anti-b5 antiserum in b5b5 homozygous rabbits fostered in uteri of 06’ homozygous mothers: compensation by allotypes at other loci. J. Immunol. 103: 629, 1969.PubMedGoogle Scholar
  49. 49.
    Wilkinson, J. M.: Variation in the N-terminal sequence of heavy chains of immunoglobulin G from rabbits of different allotype.Biochem. J. 112: 173, 1969.PubMedGoogle Scholar
  50. 50.
    Young-Cooper, G. O., and R. G. Mage: Neutralization of allotype suppression in rabbits. Immunology 26: 809, 1974.PubMedGoogle Scholar

Copyright information

© Federation of American Societies 1975

Authors and Affiliations

  • Rose G. Mage
    • 1
  1. 1.Laboratory of ImmunologyNational Institute of Allergy and Infectious Diseases National Institutes of HealthBethesdaUSA

Personalised recommendations