Abstract
Three distinct classes of κ light polypeptide chains have been detected immunochemically by an antiserum (R185) prepared against a κ Bence Jones protein with a glutamyl amino terminal residue. This antiserum had specificity for κ light chains with glutamyl amino terminal residues and differentiated κ-chains with aspartyl amino terminal residues into two classes: the three κ-chain classes have been designated as κglu, κaspII, and κaspI. The ability of antiserum R185 to detect these antigenic differences on the intact immunoglobulin molecule, as well as on the isolated light chain or Bence Jones protein, made feasible the direct classification of type K myeloma proteins and M-macroglobulins (Waldenström). The multispecificity of the antiserum permitted the quantitation of type κglu light chains in normal, hypergammaglobulinemic, and hypogammaglobulinemic sera. Whereas the distribution of myeloma proteins and Bence Jones proteins in the κglu class correlated with the distribution of κglu chains in normal and hypergammaglobulinemic sera, the M-macroglobulins in the κglu class represented 90% of the total M-macroglobulins tested and revealed a marked divergence from the range of 24–31% of κglu immunoglobulins in normal sera. A preponderance of κglu chains was detected in the sera from patients with non-sex-linked hypogammaglobulinemia and represented 60–77% of the total type K light chain content. The controlled cleavage of a Bence Jones protein representative of each κ-chain class into its variant half and constant half made possible the localization on the light polypeptide chain, the reactive sites for which antiserum R185 had specificity. The correlations between immunochemical and structural classification of κ light chains are discussed.
Full Text
The Full Text of this article is available as a PDF (1,013.7 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baglioni C., Alescio Zonta L., Cioli D., Carbonara A. Allelic antigenic factor Inv(a) of the light chains of human immunoglobulins: chemical basis. Science. 1966 Jun 10;152(3728):1517–1519. doi: 10.1126/science.152.3728.1517. [DOI] [PubMed] [Google Scholar]
- Cohen S., Porter R. R. Heterogeneity of the peptide chains of gamma-globulin. Biochem J. 1964 Feb;90(2):278–284. doi: 10.1042/bj0900278. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EDELMAN G. M., GALLY J. A. The nature of Bence-Jones proteins. Chemical similarities to polypetide chains of myeloma globulins and normal gamma-globulins. J Exp Med. 1962 Aug 1;116:207–227. doi: 10.1084/jem.116.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EDELMAN G. M., POULIK M. D. Studies on structural units of the gamma-globulins. J Exp Med. 1961 May 1;113:861–884. doi: 10.1084/jem.113.5.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EPSTEIN W. V., GROSS D. NATURALLY OCCURRING HUMAN ANTIBODY REACTING WITH BENCE JONES PROTEINS. J Exp Med. 1964 Nov 1;120:733–745. doi: 10.1084/jem.120.5.733. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- Fahey J. L., Solomon A. TWO TYPES OF gamma-MYELOMA PROTEINS, beta(2A)-MYELOMA PROTEINS, gamma(1)-MACROGLOBULINS, AND BENCE JONES PROTEINS IDENTIFIED BY TWO GROUPS OF COMMON ANTIGENIC DETERMINANTS. J Clin Invest. 1963 Jun;42(6):811–822. doi: 10.1172/JCI104773. [DOI] [PMC free article] [PubMed] [Google Scholar]
- GREY H. M., KUNKEL H. G. H CHAIN SUBGROUPS OF MYELOMA PROTEINS AND NORMAL 7S GAMMA-GLOBULIN. J Exp Med. 1964 Aug 1;120:253–266. doi: 10.1084/jem.120.2.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Harboe M., Lind K. Light chain types of transiently occurring cold haemagglutinins. Scand J Haematol. 1966;3(4):269–276. doi: 10.1111/j.1600-0609.1966.tb02371.x. [DOI] [PubMed] [Google Scholar]
- 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]
- KORNGOLD L., LIPARI R. Multiple-myeloma proteins. III. The antigenic relationship of Bence Jones proteins to normal gammaglobulin and multiple-myeloma serum proteins. Cancer. 1956 Mar-Apr;9(2):262–272. doi: 10.1002/1097-0142(195603/04)9:2<262::aid-cncr2820090210>3.0.co;2-b. [DOI] [PubMed] [Google Scholar]
- KUNKEL H. G. Zone electrophoresis. Methods Biochem Anal. 1954;1:141–170. doi: 10.1002/9780470110171.ch6. [DOI] [PubMed] [Google Scholar]
- 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]
- Lennox E. S., Cohn M. Immunoglobulins. Annu Rev Biochem. 1967;36:365–406. doi: 10.1146/annurev.bi.36.070167.002053. [DOI] [PubMed] [Google Scholar]
- Litwin S. D., Kunkel H. G. The relationship between the Inv (1) and (2) genetic antigens of kappa human light chains. J Immunol. 1967 Sep;99(3):603–609. [PubMed] [Google Scholar]
- 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]
- Merrill D., Hartley T. F., Claman H. N. Electroimmunodiffusion (EID): a simple, rapid method for quantitation of immunoglobulins in dilute biological fluids. J Lab Clin Med. 1967 Jan;69(1):151–159. [PubMed] [Google Scholar]
- Milstein C. Immunoglobulin kappa-chains. Comparative sequences in selected stretches of Bence-Jones proteins. Biochem J. 1966 Nov;101(2):352–368. doi: 10.1042/bj1010352. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Milstein C. Linked groups of residues in immunoglobulin k chains. Nature. 1967 Oct 28;216(5113):330–332. doi: 10.1038/216330a0. [DOI] [PubMed] [Google Scholar]
- Milstein C., Milstein C. P., Feinstein A. Non-allelic nature of the basic sequences of normal immunoglobulin K chains. Nature. 1969 Jan 11;221(5176):151–154. doi: 10.1038/221151a0. [DOI] [PubMed] [Google Scholar]
- Milstein C. Variations in amino-acid sequence near the disulphide bridges of Bence-Jones proteins. Nature. 1966 Jan 22;209(5021):370–373. doi: 10.1038/209370a0. [DOI] [PubMed] [Google Scholar]
- Nachman R. L., Engle R. L., Jr, Stein S. Subtypes of Bence-Jones proteins. J Immunol. 1965 Aug;95(2):295–299. [PubMed] [Google Scholar]
- Niall H. D., Edman P. Two structurally distinct classes of kappa-chains in human immunoglobulins. Nature. 1967 Oct 21;216(5112):262–263. doi: 10.1038/216262a0. [DOI] [PubMed] [Google Scholar]
- PUTMAN F. W. Structural relationships among normal human gamma-globulin, myeloma globulins, and Bence-Jones proteins. Biochim Biophys Acta. 1962 Oct 8;63:539–541. doi: 10.1016/0006-3002(62)90128-2. [DOI] [PubMed] [Google Scholar]
- PUTNAM F. W., EASLEY C. W. STRUCTURAL STUDIES OF THE IMMUNOGLOBULINS. I. THE TRYPTIC PEPTIDES OF BENCE-JONES PROTEINS. J Biol Chem. 1965 Apr;240:1626–1638. [PubMed] [Google Scholar]
- Putnam F. W., Titani K., Whitley E., Jr Chemical structure of light chains: amino acid sequence of type K Bence-Jones proteins. Proc R Soc Lond B Biol Sci. 1966 Nov 22;166(1003):124–137. doi: 10.1098/rspb.1966.0088. [DOI] [PubMed] [Google Scholar]
- Ruffilli A., Baglioni C. Subgroups of L type Bence-Jones proteins. J Immunol. 1967 Apr;98(4):874–880. [PubMed] [Google Scholar]
- Solomon A., McLaughlin C. L. Bence-Jones proteins and light chains of immunoglobulins. I. Formation and characterization of amino-terminal (variant) and carboxyl-terminal (constant) halves. J Biol Chem. 1969 Jun 25;244(12):3393–3404. [PubMed] [Google Scholar]
- Steinberg A. G., Rostenberg I. Inv(1) allotype: effect of immunoglobulin G heavy chain subtype on its expression. Science. 1969 May 30;164(3883):1072–1073. doi: 10.1126/science.164.3883.1072. [DOI] [PubMed] [Google Scholar]
- Suter L., Barnikol H. U., Watanabe S., Hilschmann N. Die Primärstruktur einer monoklonale Immunglobulin-L-Kette der Subgruppe 3 vom kappa-Typ (Bence-Jones Protein TI) Hoppe Seylers Z Physiol Chem. 1969 Feb;350(2):275–278. [PubMed] [Google Scholar]
- Tischendorf F. W., Osserman E. F. Two antigenic subtypes of human lambda immunoglobulin chains. J Immunol. 1969 Jan;102(1):172–178. [PubMed] [Google Scholar]