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One cell-one immunoglobulin. Origin of limited heterogeneity of myeloma proteins.

The Biochemical Journal, 01 Jan 1970, 116(2):241-248
https://doi.org/10.1042/bj1160241 PMID: 5414099 PMCID: PMC1185352

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Abstract 

Plasma-cell tumour 5563 forms a single molecular species of immunoglobulin IgG(2)a, i.e. one variant of heavy chain and one variant of light chain. The molecules formed are labile and undergo alterations in charge properties, which rapidly lead to heterogeneity of the myeloma protein after synthesis. The single immunoglobulin species originally formed is found only after the shortest time-intervals tested, i.e. 10min incubation. Two types of changes in charge properties take place: (1) The originally formed protein (component o) is converted via an intermediate o' into the most basic form of 5563 myeloma protein found in serum (component a). Charge differences between these components are suppressed at pH8.9, but can be studied by chromatography at pH6.5 or by analysis of isoelectric points by isoelectric focusing in polyacrylamide gel. The conversion of components o and o' into component a apparently commences soon after assembly of the molecules and proceeds to completion extracellularly. (2) The second type of charge difference that distinguishes components a, b, c and d is exhibited over the pH range 6.0-8.9, but not at acid pH, and has been studied by electrophoresis at pH8.9, by chromatography and by isoelectric focusing. Conversion of component a into components b, c, d and e is only partial so that all five components can be found at decreasing concentrations in serum. Both types of charge alteration can be effected in vitro in the presence of serum, with optimum pH8.0. None of the charge differences could be attributed to the secretion process, since a component with the same isoelectric point as component o was found in secreted myeloma protein (1h). We have found no evidence to support the idea that the first type of change from component o to component a is due to ring formation of N-terminal [(14)C]glutamine into pyrrolid-2-one-5-carboxylic acid; however, our findings do not exclude this process happening very rapidly to a precursor of component o, possibly the polypeptide chain during or immediately after synthesis. In studying this point we noted that not only the heavy chains but also the kappa-type light chain of mouse 5563 myeloma protein have a blocked N-terminus.

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Biochem J. 1970 Jan; 116(2): 241–248.
PMCID: PMC1185352
PMID: 5414099

One cell–one immunoglobin. Origin of limited heterogeneity of myeloma proteins

Z. L. Awdeh,* A. R. Williamson, and Brigitte A. Askonas
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Abstract

Plasma-cell tumour 5563 forms a single molecular species of immunoglobulin IgG2a, i.e. one variant of heavy chain and one variant of light chain. The molecules formed are labile and undergo alterations in charge properties, which rapidly lead to heterogeneity of the myeloma protein after synthesis. The single immunoglobulin species originally formed is found only after the shortest time-intervals tested, i.e. 10min incubation. Two types of changes in charge properties take place: (1) The originally formed protein (component o) is converted via an intermediate o′ into the most basic form of 5563 myeloma protein found in serum (component a). Charge differences between these components are suppressed at pH8.9, but can be studied by chromatography at pH6.5 or by analysis of isoelectric points by isoelectric focusing in polyacrylamide gel. The conversion of components o and o′ into component a apparently commences soon after assembly of the molecules and proceeds to completion extracellularly. (2) The second type of charge difference that distinguishes components a, b, c and d is exhibited over the pH range 6.0–8.9, but not at acid pH, and has been studied by electrophoresis at pH8.9, by chromatography and by isoelectric focusing. Conversion of component a into components b, c, d and e is only partial so that all five components can be found at decreasing concentrations in serum. Both types of charge alteration can be effected in vitro in the presence of serum, with optimum pH8.0. None of the charge differences could be attributed to the secretion process, since a component with the same isoelectric point as component o was found in secreted myeloma protein (1h). We have found no evidence to support the idea that the first type of change from component o to component a is due to ring formation of N-terminal [14C]glutamine into pyrrolid-2-one-5-carboxylic acid; however, our findings do not exclude this process happening very rapidly to a precursor of component o, possibly the polypeptide chain during or immediately after synthesis. In studying this point we noted that not only the heavy chains but also the κ-type light chain of mouse 5563 myeloma protein have a blocked N-terminus.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • ASKONAS BA. A study on globulin formation by plasma-cell neoplasm (5563) transplantable in mice. Biochem J. 1961 Apr;79:33–43. [Europe PMC free article] [Abstract] [Google Scholar]
  • Awdeh ZL, Askonas BA, Williamson AR. The homogeneous-gamma-G-immunoglobulin produced by mouse plasmacytoma 5563 and its subsequent heterogeneity in serum. Biochem J. 1967 Feb;102(2):548–553. [Europe PMC free article] [Abstract] [Google Scholar]
  • Awdeh ZL, Williamson AR, Askonas BA. Isoelectric focusing in polyacrylamide gel and its application to immunoglobulins. Nature. 1968 Jul 6;219(5149):66–67. [Abstract] [Google Scholar]
  • Awdeh ZL, Williamson AR, Askonas BA. Heavy and light chains of a homogeneous immunoglobulin-G. FEBS Lett. 1969 Nov 29;5(4):275–278. [Abstract] [Google Scholar]
  • Bernfield MR, Nestor L. The enzymatic conversion of glutaminyl-tRNA to pyrrolidone carboxylate-tRNA. Biochem Biophys Res Commun. 1968 Dec 9;33(5):843–849. [Abstract] [Google Scholar]
  • Cebra JJ, Colberg JE, Dray S. Rabbit lymphoid cells differentiated with respect to alpha-, gamma-, and mu- heavy polypeptide chains and to allotypic markers Aa1 and Aa2. J Exp Med. 1966 Mar 1;123(3):547–558. [Europe PMC free article] [Abstract] [Google Scholar]
  • Chrambach A, Reisfeld RA, Wyckoff M, Zaccari J. A procedure for rapid and sensitive staining of protein fractionated by polyacrylamide gel electrophoresis. Anal Biochem. 1967 Jul;20(1):150–154. [Abstract] [Google Scholar]
  • Feinstein A. Use of charged thiol reagents in interpreting the electrophoretic patterns of immune globulin chains and fragments. Nature. 1966 Apr 9;210(5032):135–137. [Abstract] [Google Scholar]
  • FLEISCHMAN JB, PAIN RH, PORTER RR. Reduction of gamma-globulins. Arch Biochem Biophys. 1962 Sep;Suppl 1:174–180. [Abstract] [Google Scholar]
  • LEVY AL. A paper chromatographic method for the quantitative estimation of amino-acids. Nature. 1954 Jul 17;174(4420):126–127. [Abstract] [Google Scholar]
  • Moav B, Harris TN. Pyrrolid-2-one-5 carboxylic acid involvement in the biosynthesis of rabbit immunoglobulin. Biochem Biophys Res Commun. 1967 Dec 15;29(5):773–776. [Abstract] [Google Scholar]
  • Notani GW, Munro AJ, Knopf PM. A charge difference between an intracellular and secreted mouse myeloma globulin. Biochem Biophys Res Commun. 1966 Nov 22;25(4):395–401. [Abstract] [Google Scholar]
  • Perham R, Appella E, Potter M. Light chains of mouse myeloma proteins: partial amino acid sequence. Science. 1966 Oct 21;154(3747):391–393. [Abstract] [Google Scholar]
  • Pernis B, Chiappino G, Kelus AS, Gell PG. Cellular localization of immunoglobulins with different allotypic specificities in rabbit lymphoid tissues. J Exp Med. 1965 Nov 1;122(5):853–876. [Europe PMC free article] [Abstract] [Google Scholar]
  • Press EM, Piggot PJ, Porter RR. The N- and c-terminal amino acid sequences of the heavy chain from a pathological human immunoglobulin IgG. Biochem J. 1966 May;99(2):356–366. [Europe PMC free article] [Abstract] [Google Scholar]
  • Robert B, Bockman RS. Studies on the proteolytic activity of gamma-globulin preparations. Biochem J. 1967 Feb;102(2):554–563. [Europe PMC free article] [Abstract] [Google Scholar]
  • Rüde E, Givol D. A blocked N-terminal residue in the light chain of rabbit immunoglobulin G. Biochem J. 1968 Apr;107(4):449–453. [Europe PMC free article] [Abstract] [Google Scholar]
  • Williamson AR, Askonas BA. Biosynthesis of immunoglobulins: the separate classes of polyribosomes synthesizing heavy and light chains. J Mol Biol. 1967 Jan 28;23(2):201–216. [Abstract] [Google Scholar]
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