scholarly journals BENCE JONES PROTEINS AND LIGHT CHAINS OF IMMUNOGLOBULINS

1969 ◽  
Vol 130 (6) ◽  
pp. 1295-1311 ◽  
Author(s):  
Alan Solomon ◽  
Carla L. McLaughlin
Keyword(s):  
Light Chain ◽  
Light Chains ◽  
Bence Jones Protein ◽  
Amino Terminal ◽  
Type K ◽  
Myeloma Proteins ◽  
Immunoglobulin Molecule ◽  
Polypeptide Chains ◽  
Bence Jones Proteins

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.

Chemical structure of light chains: amino acid sequence of type K Bence-Jones proteins

1966 ◽  
Vol 166 (1003) ◽  
pp. 124-137 ◽  
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Sequence Data ◽  
Single Point ◽  
Structural Difference ◽  
Light Chains ◽  
Single Point Mutation ◽  
Amino Terminal ◽  
Type K ◽  
Bence Jones Proteins

Bence-Jones proteins are the light chains of the autologous myeloma globulin and are analogous to the light chains of normal human immunoglobulins. Peptide mapping has demonstrated that Bence-Jones proteins share a fixed portion of their sequence (the ‘constant’ portion) and also have a mutable part (the ‘variable’ portion). Sequence analysis and ordering of the tryptic and chymotryptic peptides has provided the tentative complete amino acid sequence of one Bence-Jones protein of antigenic type K. Comparison with partial sequence data for other type K Bence-Jones proteins has revealed many structural differences in the amino terminal half of the molecules, but only one structural difference in the carboxyl terminal half. The latter is strongly correlated with the Inv genetic factor. The points of interchange in the amino terminal half occur in clusters close to the half cystine residues and the ‘switch peptide’ (positions 102 through 105), after which the sequence becomes essentially invariant. This suggests that the major areas subject to sequence variation are part of a single topographical region which may define a portion of the antigen combining site in the light chains of antibodies. Many, but not all, the amino acid interchanges are compatible with a single point mutation. As yet, no single mutational theory suffices to explain the manifold differences in structure of the light chains. Such structural variation, however, could result from the presence of many related genes.

scholarly journals COMPARISONS OF BENCE-JONES PROTEINS AND L POLYPEPTIDE CHAINS OF MYELOMA GLOBULINS AFTER HYDROLYSIS WITH TRYPSIN

1963 ◽  
Vol 118 (1) ◽  
pp. 41-53 ◽  
Author(s):  
J. H. Schwartz ◽  
G. M. Edelman
Keyword(s):  
High Voltage ◽  
Two Dimensional ◽  
Bence Jones Protein ◽  
Myeloma Protein ◽  
Myeloma Proteins ◽  
Group I ◽  
Chain Fraction ◽  
Polypeptide Chains ◽  
High Voltage Electrophoresis ◽  
Bence Jones Proteins

L polypeptide chains of myeloma globulin and Bence-Jones protein isolated from the same patient were found to be identical after comparison of their tryptic hydrolysates by two-dimensional high voltage electrophoresis. The patterns of peptides from proteins belonging to antigenic group I differed markedly from those of proteins in antigenic group II. A partially purified H chain fraction was compared with L chains from the same myeloma protein. The tryptic hydrolysates yielded dissimilar patterns of peptides. These data indicate that γ-myeloma proteins contain two kinds of polypeptide chains, Hγ chains and either LI or LII chains. The L chains appear to be identical with those comprising the Bence-Jones protein from the same patient.

Historical perspectives in clinical pathology: Bence Jones protein—early urine chemistry and the impact on modern day diagnostics

2020 ◽  
pp. jclinpath-2020-206675
Author(s):  
Sheromna Sewpersad ◽  
Tahir S Pillay
Keyword(s):  
Light Chain ◽  
Clinical Pathology ◽  
Light Chains ◽  
Immunoglobulin Light Chains ◽  
Bence Jones Protein ◽  
Historical Perspectives ◽  
Serum Free Light Chain ◽  
The Impact ◽  
Made In ◽  
Bence Jones Proteins

This is the third in the series of historical articles dealing with developments in clinical pathology. Bence Jones proteins are immunoglobulin light chains found in excessive quantities in urine in multiple myeloma and are believed to be one of the first tumour markers ever discovered . Dr Henry Bence Jones is credited with the discovery of this protein in 1847 that bears his name and he can also be regarded as the first chemical pathologist/clinical chemist. Since then, numerous advances and refinements have been made in the measurement and detection of urine light chain proteins which have resulted in the current sensitive serum free light chain assays used today.

scholarly journals Dissociation of ϰ- and λ-chains from reduced human immunoglobulins

1965 ◽  
Vol 97 (2) ◽  
pp. 460-465 ◽  
Author(s):  
S Cohen ◽  
S Gordon
Keyword(s):  
Amino Acid ◽  
Amino Acid Composition ◽  
Acid Composition ◽  
Light Chain ◽  
Human Immunoglobulin ◽  
Light Chains ◽  
Type K ◽  
Human Immunoglobulins ◽  
Starch Gels ◽  
Bence Jones Proteins

1. The light chains of human immunoglobulin (Ig) exist in two forms, kappa (type K) and lambda (type L). The two types of chains can be partially separated by taking advantage of the fact that lambda-chains, for the most part, dissociate from reduced Ig at higher pH than do the kappa-chains. The same difference in dissociation of type K and L chains was observed with myeloma IgG and IgA proteins, but not with pathological IgM proteins. 2. When analysed in urea-glycine starch gels, pH7, both kappa- and lambda-chains show ten electrophoretic bands having the same mobilities as those of the whole light-chain subfractions. Normal kappa- and lambda-chains show similar differences in overall amino acid composition to those previously found with myeloma kappa- and lambda-chains and type K and L Bence-Jones proteins.

scholarly journals PROTEIN-PROTEIN INTERACTIONS AMONG L POLYPEPTIDE CHAINS OF BENCE-JONES PROTEINS AND HUMAN γ-GLOBULINS

1964 ◽  
Vol 119 (5) ◽  
pp. 817-836 ◽  
Author(s):  
J. A. Gally ◽  
G. M. Edelman
Keyword(s):  
Protein Interactions ◽  
Protein Protein Interactions ◽  
Bence Jones Protein ◽  
Thermally Induced ◽  
Myeloma Proteins ◽  
Group I ◽  
Γ Globulins ◽  
Normal Human ◽  
Polypeptide Chains ◽  
Bence Jones Proteins

The L polypeptide chains of certain Bence-Jones proteins of group I have been found in three forms: monomers of molecular weight of about 20,000, dimers which monomerize in dissociating solvents, and dimers which are stable in such solvents. The L polypeptide chains of some Bence-Jones proteins of group II were found to occur naturally only as stable dimers. The L chains of normal human γ-globulin have been obtained in a reduced unalkylated form, and a fraction of these chains was found to form stable dimers under oxidizing conditions. It is suggested that a single disulfide bond is involved in stabilization of the dimer. In experiments on the reconstitution of 7S γ-globulin, it was found that stable dimers of L polypeptide chains did not associate appreciably with Hγ chains to form a soluble product. L chains in the monomeric form, both of a reduced alkylated Bence-Jones protein and of reduced unalkylated γ-globulin, combined with Hγ chains to form a 7S product. After hydrolysis with papain, the 7S material containing the Bence-Jones L chains yielded fragments comparable to the fragments of papain-treated myeloma proteins. As indicated by spectrofluorometric measurements, dissociable dimers and stable dimers of the L chains of a Bence-Jones protein both underwent identical thermally induced transitions in the temperature range 48–58°C. When L polypeptide chains were present in reduced alkylated γ-globulin or reduced alkylated S fragments, no transition occurred until 65°C, the coagulation temperature of γ-globulin and S fragments. Above this temperature, L chains were released into solution. These experiments suggested that free L chains and L chains bound to Hγ chains have different conformational stabilities.

scholarly journals Functional roles of two polypeptide chains that compose an antigen-specific suppressor T cell factor.

1984 ◽  
Vol 159 (4) ◽  
pp. 1096-1104 ◽  
Author(s):  
M Taniguchi ◽  
T Tokuhisa ◽  
T Itoh ◽  
M Kanno
Keyword(s):  
T Cell ◽  
Light Chain ◽  
Mrna Translation ◽  
Functional Expression ◽  
Light Chains ◽  
Antigen Specificity ◽  
Suppressor Factor ◽  
Functional Roles ◽  
T Cell Factor ◽  
Polypeptide Chains

The functional roles of the two polypeptide chains that compose the T cell suppressor factor (TsF) that mediates the antigen-specific and genetically restricted suppressor function were studied by using the heavy or light chains isolated from the conventional TsF or the 11S and 13S mRNA translation products of TsF. Either the heavy or the light chain of mRNA translation products reconstitutes the active TsF that suppresses the antibody response in an antigen-specific and genetically restricted manner when it is combined with the isolated heavy or light chain from the conventional TsF. As a consequence, the antigen-binding heavy chain mediates the antigen specificity of TsF. On the other hand, the I-J-positive light chain works as an element to determine the genetic restriction specificity. Thus, the identity of the histocompatibility between the I-J haplotypes on the light chain and the responding cell is essential for the functional expression of TsF. No genetic preference, however, was observed, in the association of the heavy and light chains of TsF.

scholarly journals A major group of mouse kappa chains controlled by the chromosome 6 locus, IgK-Ef2.

1980 ◽  
Vol 152 (3) ◽  
pp. 555-564 ◽  
Author(s):  
C Lazure ◽  
W T Hum ◽  
D M Gibson
Keyword(s):  
Light Chain ◽  
Normal Mouse ◽  
Variable Region ◽  
Normal Serum ◽  
Light Chains ◽  
Mouse Serum ◽  
Chromosome 6 ◽  
Frequency Of Occurrence ◽  
Myeloma Proteins ◽  
Normal Light

We previously demonstrated that loci closely linked to the Ly-3 locus control the expression of distinct sets of light chains in normal mouse serum immunoglobulin. One of these loci, IgK-Ef2, was shown to control two major bands in normal light chain isoelectric focusing (IF) profiles. Strains possessing the marker bands were designated IgK-Ef2a. Screening of myeloma proteins from the strains BALB/c (IgK-Ef2a) and NZB (IgK-Ef2b) led to the identification of eight proteins in the BALB/c collection having light chains that cofocus precisely with the polymorphic IF bands observed in normal serum light chains. Partial sequence analysis of 3 of the light chains has shown that they are all identical in the first 30 positions, which indicates that they constitute a single variable region of the kappa light chain (VK) group (VK1). The frequency of occurrence of the group within the BALB/c myeloma collections (8 out of 277) suggests that the number of such groups may be closer to 50 than to 100. The finding supports an interpretation of the genetic polymorphism as being in part a result of the absence of genes related to VK1 in IgK-Ef2b strains of mice.

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

1966 ◽  
Vol 124 (2) ◽  
pp. 185-197 ◽  
Author(s):  
Robert A. Prendergast ◽  
Howard M. Grey ◽  
Henry G. Kunkel
Keyword(s):  
Electrophoretic Mobility ◽  
Quaternary Structure ◽  
Antigenic Specificity ◽  
Light Chains ◽  
Antigenic Analysis ◽  
Naturally Occurring ◽  
Myeloma Proteins ◽  
Hybrid Molecules ◽  
Noncovalent Bonds ◽  
Polypeptide Chains

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.

Amyloidosis and Light Chain Plasmocytoma

1976 ◽  
Vol 62 (2) ◽  
pp. 219-226 ◽  
Author(s):  
Giovanna Tosato ◽  
Enzo Fagiolo
Keyword(s):  
Bone Marrow ◽  
Light Chain ◽  
Light Chains ◽  
Primary Amyloidosis ◽  
Intercellular Substance ◽  
Osteolytic Lesions ◽  
Small Areas ◽  
Type K ◽  
Amyloid Deposits ◽  
Initial Symptoms

Nine cases of light chain plasmocytomas, 6 type λ and 3 type k, have been studied in reference to amyloid presence and localisation. Bone marrow plasmocytosis, light chains in serum and/or in the urine, and osteolytic lesions were demonstrated in all the patients. Initial symptoms, i.e., macroglossia and lymphadenopathy, were secondary to amyloid deposits in two patients; the absence of overt evidence of plasmocytoma had previously led to the diagnosis of « primary » amyloidosis in one case. Amyloidosis may therefore be associated with concealed plasmocytomas, evident only after a certain period of time. Amyloidosis was not detected in the sites where it was clinically suspected in two cases. However, on bone marrow aspirates, amyloid was present in seven patients where thioflavine T appeared as homogeneous, amorphous, intercellular substance localised in small areas.

Sign in / Sign up

Export Citation Format

Share Document