Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1966 Aug 1;124(2):185–197. doi: 10.1084/jem.124.2.185

RECOMBINATION OF HEAVY AND LIGHT CHAINS OF HUMAN γA-MYELOMA PROTEINS: FORMATION OF HYBRID MOLECULES AND CONFIGURATIONAL SPECIFICITY

Robert A Prendergast 1, Howard M Grey 1, Henry G Kunkel 1
PMCID: PMC2180477  PMID: 4162153

Abstract

The present studies demonstrate that the conditions necessary for reductive cleavage, isolation, and recombination of L and H polypeptide chains of human γA-myeloma globulins parallel those required for similar manipulation of the component chains of γG-globulin. Specificity of recombination was shown for chains derived from the same protein. In contrast, no intradass preferential recombination was demonstrable. Hybrid molecules, formed by reassociation of noncovalent bonds, could be synthesized from isolated chains of two immunoglobulin classes resulting in the formation of molecules of the type γA-H-γG-L and γG-H-γA-L. Several sera containing both γA- and γG-"monoclonal" peaks were studied, one of which demonstrated the L chains associated with both peaks to be identical both by electrophoretic mobility in acid-urea gel and antigenic analysis. The possibility is considered that this case represents a naturally occurring analogue of the artificially produced hybrid molecules described in this study. Configurational antigenic specificity of γA-myeloma proteins, imposed by the presence of kappa L chains in native and appropriately recombined molecules, provides a further indication of the importance of noncovalent bonds in the establishment of the quaternary structure of these proteins.

Full Text

The Full Text of this article is available as a PDF (639.1 KB).

Selected References

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

  1. BACHMANN R. SIMULTANEOUS OCCURRENCE OF TWO IMMUNOLOGICALLY DIFFERENT M-COMPONENTS IN SERUM. Acta Med Scand. 1965 May;177:593–599. doi: 10.1111/j.0954-6820.1965.tb01868.x. [DOI] [PubMed] [Google Scholar]
  2. FAHEY J. L. TWO TYPES OF 6.6 S GAMMA-GLOBULINS, BETA-2A-GLOBULINS AND 18 S GAMMA 1-MACROGLOBULINS IN NORMAL SERUM AND GAMMA-MICROGLOBULINS IN NORMAL URINE. J Immunol. 1963 Oct;91:438–447. [PubMed] [Google Scholar]
  3. 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]
  4. FRANEK F., NEZLIN R. S. Recovery of antibody combining activity by interaction of different peptide chains isolated from purified horse antitoxins. Folia Microbiol (Praha) 1963 Mar;8:128–130. doi: 10.1007/BF02877236. [DOI] [PubMed] [Google Scholar]
  5. FRANGIONE B., FRANKLIN E. C. STRUCTURAL STUDIES OF HUMAN IMMUNOGLOBULINS. DIFFERENCES IN THE FD FRAGMENTS OF THE HEAVY CHAINS OF G MYELOMA PROTEINS. J Exp Med. 1965 Jul 1;122:1–10. doi: 10.1084/jem.122.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. GREY H. M., MANNIK M., KUNKEL H. G. INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS. CHARACTERISTICS AND LOCALIZATION TO SUBUNITS. J Exp Med. 1965 Apr 1;121:561–575. doi: 10.1084/jem.121.4.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Grey H. M., Mannik M. Specificity of recombination of H and L chains from human gamma-G-myeloma proteins. J Exp Med. 1965 Sep 1;122(3):619–632. doi: 10.1084/jem.122.3.619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. HELMKAMP R. W., GOODLAND R. L., BALE W. F., SPAR I. L., MUTSCHLER L. E. High specific activity iodination of gamma-globulin with iodine-131 monochloride. Cancer Res. 1960 Nov;20:1495–1500. [PubMed] [Google Scholar]
  9. Hilschmann N., Craig L. C. Amino acid sequence studies with Bence-Jones proteins. Proc Natl Acad Sci U S A. 1965 Jun;53(6):1403–1409. doi: 10.1073/pnas.53.6.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. KUNKEL H. G., ALLEN J. C., GREY H. M. GENETIC CHARACTERS AND THE POLYPEPTIDE CHAINS OF VARIOUS TYPES OF GAMMA-GLOBULIN. Cold Spring Harb Symp Quant Biol. 1964;29:443–447. doi: 10.1101/sqb.1964.029.01.046. [DOI] [PubMed] [Google Scholar]
  11. KUNKEL H. G. Zone electrophoresis. Methods Biochem Anal. 1954;1:141–170. doi: 10.1002/9780470110171.ch6. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Mannik M., Kunkel H. G. CLASSIFICATION OF MYELOMA PROTEINS, BENCE JONES PROTEINS, AND MACROGLOBULINS INTO TWO GROUPS ON THE BASIS OF COMMON ANTIGENIC CHARACTERS. J Exp Med. 1962 Nov 30;116(6):859–877. doi: 10.1084/jem.116.6.859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. OLINS D. E., EDELMAN G. M. RECONSTITUTION OF 7S MOLECULES FROM L AND H POLYPEPTIDE CHAINS OF ANTIBODIES AND GAMMA-GLOBULINS. J Exp Med. 1964 May 1;119:789–815. doi: 10.1084/jem.119.5.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. ROHOLT O., ONOUE K., PRESSMAN D. SPECIFIC COMBINATION OF H AND L CHAINS OF RABBIT GAMMA-GLOBULINS. Proc Natl Acad Sci U S A. 1964 Feb;51:173–178. doi: 10.1073/pnas.51.2.173. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES