Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1973 Aug 1;138(2):410–427. doi: 10.1084/jem.138.2.410

PHYLOGENETICALLY ASSOCIATED RESIDUES WITHIN THE VHIII SUBGROUP OF SEVERAL MAMMALIAN SPECIES

EVIDENCE FOR A "PAUCI-GENE" BASIS FOR ANTIBODY DIVERSITY

J Donald Capra 1, Richard L Wasserman 1, J Michael Kehoe 1
PMCID: PMC2139396  PMID: 4198201

Abstract

Immunoglobulin heavy chains from IgG pools of several mammalian species have been subjected to Edman degradation on an automated protein sequencer. The percentage of unblocked vs. blocked heavy chains was estimated from the yield of the invariant valine in the second position. Further analysis of these unblocked polypeptides unequivocally placed them in the VHIII subgroup on the basis of homology with known human heavy chain sequences. The mammals studied could be divided into three distinct categories on the basis of the distribution of the VHIII subgroup. In several species the VHIII subgroup could not be detected while, in others, virtually all of the heavy chains belonged to this subgroup. Several species had intermediate amounts with the level of the VHIII subgroup restricted to between 19 and 29% of the total pool. Within experimental error, all members of a given order had a similar VHIII subgroup distribution. Further amino acid sequence studies illustrated a high degree of structural homogeneity in the heavy chains of IgG isolated from pooled sera of a number of mammalian species. The very close amino acid sequence homologies of the amino terminal 24 residues of the various pools corroborated conclusions previously obtained using several myeloma proteins from some of these same species. In particular, certain phylogenetically associated residues were identifiable at characteristic positions in the pools in confirmation of their identification in the myeloma proteins. The simplest assumptions would suggest that these findings are more compatible with a pauci-gene than a multi-gene basis for the generation of antibody diversity.

Full Text

The Full Text of this article is available as a PDF (978.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bourgois Alain, Fougereau Michel. Partial amino acid sequence of the variable region of a mouse gammaG2a immunoglobulin heavy chain. Evidence for the existence of a third sub-group of variability for the heavy chain pool. FEBS Lett. 1970 Jun 27;8(5):265–268. doi: 10.1016/0014-5793(70)80283-6. [DOI] [PubMed] [Google Scholar]
  2. Brenner S., Milstein C. Origin of antibody variation. Nature. 1966 Jul 16;211(5046):242–243. doi: 10.1038/211242a0. [DOI] [PubMed] [Google Scholar]
  3. Cohn M. The take-home lesson--1971. Ann N Y Acad Sci. 1971 Dec 31;190:529–584. doi: 10.1111/j.1749-6632.1971.tb13562.x. [DOI] [PubMed] [Google Scholar]
  4. Delovitch T. L., Baglioni C. Estimation of light-chain gene reiteration of mouse immunoglobulin by DNA-RNA hybridization. Proc Natl Acad Sci U S A. 1973 Jan;70(1):173–178. doi: 10.1073/pnas.70.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dreyer W. J., Bennett J. C. The molecular basis of antibody formation: a paradox. Proc Natl Acad Sci U S A. 1965 Sep;54(3):864–869. doi: 10.1073/pnas.54.3.864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Edelman G. M., Cunningham B. A., Gall W. E., Gottlieb P. D., Rutishauser U., Waxdal M. J. The covalent structure of an entire gammaG immunoglobulin molecule. Proc Natl Acad Sci U S A. 1969 May;63(1):78–85. doi: 10.1073/pnas.63.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. FLEISCHMAN J. B., PAIN R. H., PORTER R. R. Reduction of gamma-globulins. Arch Biochem Biophys. 1962 Sep;Suppl 1:174–180. [PubMed] [Google Scholar]
  8. Gally J. A., Edelman G. M. Somatic translocation of antibody genes. Nature. 1970 Jul 25;227(5256):341–348. doi: 10.1038/227341a0. [DOI] [PubMed] [Google Scholar]
  9. Hood L., Eichmann K., Lackland H., Krause R. M., Ohms J. J. Rabbit antibody light chains and gene evolution. Nature. 1970 Dec 12;228(5276):1040–1044. doi: 10.1038/2281040a0. [DOI] [PubMed] [Google Scholar]
  10. Hood L., Prahl J. The immune system: a model for differentiation in higher organisms. Adv Immunol. 1971;14:291–351. doi: 10.1016/s0065-2776(08)60287-4. [DOI] [PubMed] [Google Scholar]
  11. Hood L., Talmage D. W. Mechanism of antibody diversity: germ line basis for variability. Science. 1970 Apr 17;168(3929):325–334. doi: 10.1126/science.168.3929.325. [DOI] [PubMed] [Google Scholar]
  12. Hood L., Waterfield M. D., Morris J., Todd C. W. Light chain structure and theories of antibody diversity. Ann N Y Acad Sci. 1971 Dec 31;190:26–36. doi: 10.1111/j.1749-6632.1971.tb13521.x. [DOI] [PubMed] [Google Scholar]
  13. Kabat E. A. The paucity of species-specific amino acid residues in the variable regions of human and mouse Bence-Jones proteins and its evolutionary and genetic implications. Proc Natl Acad Sci U S A. 1967 May;57(5):1345–1349. doi: 10.1073/pnas.57.5.1345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kehoe J. M., Capra J. D. Localization of two additional hypervariable regions in immunoglobulin heavy chains. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2019–2021. doi: 10.1073/pnas.68.9.2019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kehoe J. M., Capra J. D. Sequence relationships among the variable regions of immunoglobulin heavy chains from various mammalian species. Proc Natl Acad Sci U S A. 1972 Aug;69(8):2052–2055. doi: 10.1073/pnas.69.8.2052. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kubo R. T., Rosenblum I. Y., Benedict A. A. Amino terminal sequences of heavy and light chains of chicken anti-dinitrophenyl antibody. J Immunol. 1971 Dec;107(6):1781–1784. [PubMed] [Google Scholar]
  17. Köhler H., Shimizu A., Paul C., Moore V., Putnam F. W. Three variable-gene pools common to IgM, IgG and IgA immunoglobulins. Nature. 1970 Sep 26;227(5265):1318–1320. doi: 10.1038/2271318a0. [DOI] [PubMed] [Google Scholar]
  18. Köhler H., Shimizu A., Paul C., Moore V., Putnam F. W. Three variable-gene pools common to IgM, IgG and IgA immunoglobulins. Nature. 1970 Sep 26;227(5265):1318–1320. doi: 10.1038/2271318a0. [DOI] [PubMed] [Google Scholar]
  19. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  20. Milstein C., Pink J. R. Structure and evolution of immunoglobulins. Prog Biophys Mol Biol. 1970;21:209–263. doi: 10.1016/0079-6107(70)90026-x. [DOI] [PubMed] [Google Scholar]
  21. Novotný J., Dolejs L., Franek F. Uniformity and species-specific features of the N-terminal amino-acid sequence of porcine immunoglobulin lambda-chains. Eur J Biochem. 1972 Dec 4;31(2):277–289. doi: 10.1111/j.1432-1033.1972.tb02530.x. [DOI] [PubMed] [Google Scholar]
  22. Novotný J., Dolejs L., Franek F. Uniformity and species-specific features of the N-terminal amino-acid sequence of porcine immunoglobulin lambda-chains. Eur J Biochem. 1972 Dec 4;31(2):277–289. doi: 10.1111/j.1432-1033.1972.tb02530.x. [DOI] [PubMed] [Google Scholar]
  23. Ponstingl H., Schwarz J., Reichel W., Hilschmann N. Die Primärstruktur eines monoklonalen gamma-1-Immunoglobulins (Myelomprotein NIE). I. Aminosäuresequenz des variablen Teils der H-Kette, Subgruppen variabler Teile. Hoppe Seylers Z Physiol Chem. 1970 Dec;351(12):1591–1594. [PubMed] [Google Scholar]
  24. Ray A., Cebra J. J. Localization of affinity-labeled residues in the primary structure of anti-dinitrophenyl antibody raised in strain 13 guinea pigs. Biochemistry. 1972 Sep 12;11(19):3647–3657. doi: 10.1021/bi00769a024. [DOI] [PubMed] [Google Scholar]
  25. SCHEIDEGGER J. J. Une micro-méthode de l'immuno-electrophorèse. Int Arch Allergy Appl Immunol. 1955;7(2):103–110. [PubMed] [Google Scholar]
  26. Schiechl H., Hilschmann N. Die Primärstruktur einer monoklonalen Immunglobulin-L-Kette der Subgruppe I vom kappa-Typ (Bence-Jones-Protein Au): gekoppelte Austausche innerhalb der Subgruppen. Hoppe Seylers Z Physiol Chem. 1971 Jan;352(1):111–115. [PubMed] [Google Scholar]
  27. Smithies O., Gibson D., Fanning E. M., Goodfliesh R. M., Gilman J. G., Ballantyne D. L. Quantitative procedures for use with the Edman-Begg sequenator. Partial sequences of two unusual immunoglobulin light chains, Rzf and Sac. Biochemistry. 1971 Dec 21;10(26):4912–4921. doi: 10.1021/bi00802a013. [DOI] [PubMed] [Google Scholar]
  28. Suran A. A., Papermaster B. W. N-terminal sequences of heavy and light chains of leopard shark immunoglobulins: evolutionary implications. Proc Natl Acad Sci U S A. 1967 Oct;58(4):1619–1623. doi: 10.1073/pnas.58.4.1619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wang A. C., Pink J. R., Fudenberg H. H., Ohms J. A variable region subclass of heavy chains common to immunoglobulins G, A, and M and characterized by an unblocked amino-terminal residue. Proc Natl Acad Sci U S A. 1970 Jul;66(3):657–663. doi: 10.1073/pnas.66.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wood A. E. Interrelations of humans, dogs, and rodents. Science. 1972 Apr 28;176(4033):437–437. doi: 10.1126/science.176.4033.437. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES