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.

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 THE NATURE OF BENCE-JONES PROTEINS

1962 ◽  
Vol 116 (2) ◽  
pp. 207-227 ◽  
Author(s):  
G. M. Delman ◽  
J. A. Gally
Keyword(s):  
Molecular Weight ◽  
Extensive Study ◽  
Starch Gel Electrophoresis ◽  
Bence Jones Protein ◽  
Protein Amino Acid ◽  
Myeloma Protein ◽  
Γ Globulins ◽  
Normal Human ◽  
Polypeptide Chains ◽  
Bence Jones Proteins

The chemical relations among Bence-Jones proteins, myeloma proteins, and normal γ-globulins have been investigated by a variety of means. Starch gel electrophoresis in 8 M urea of reduced alkylated Bence-Jones proteins yielded patterns of bands corresponding to those of the light (L) polypeptide chains of the dissociated myeloma protein from the same patient. One instance in which this correspondence was found was chosen for extensive study. Chromatography on carboxymethylcellulose in 6 M urea was employed to isolate the light (L) polypeptide chains and heavy (H) polypeptide chains of the completely reduced and alkylated myeloma protein. Isolation of similarly treated Bence-Jones protein from the same patient corroborated the correspondence to the L chains of the myeloma protein. Amino acid analyses indicated that the compositions of the Bence-Jones protein and the L chains of the myeloma protein were identical. Moreover, the thermosolubility properties and spectrofluorometric behavior of the isolated L chains and Bence-Jones protein were similar. Ultracentrifugal analyses of the L chains of normal human 7S γ-globulin showed that their molecular weight in 6 M urea was 20,000. In aqueous solution their molecular weight was 41,000, suggesting that they exist as dimers under these conditions. The L chains of normal human γ-globulin were found to have reversible thermosolubility properties similar to those of Bence-Jones proteins. The H chains of normal human γ-globulin did not share these properties. Using spectrofluorometric methods, characteristic molecular transitions were found upon heating Bence-Jones proteins and L chains. These transitions were indicated by an increase in the intensity of fluorescence at well defined temperatures as well as by reversible shifts in the wavelength of maximal emission. The findings suggest that Bence-Jones proteins are composed of L chains of the type found in normal and pathological γ-globu]ins.

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.

Occurrence of Myeloma-Like γ-Globulin in C.S.F of A Four-Month Old Infant with Hydrocephalus

PEDIATRICS ◽  
1964 ◽  
Vol 33 (3) ◽  
pp. 435-440
Author(s):  
G. M. HOCHWALD ◽  
G. J. THORBECKE
Keyword(s):  
Paper Electrophoresis ◽  
Reticulum Cell ◽  
Reticulum Cell Sarcoma ◽  
Myeloma Protein ◽  
Characteristic Appearance ◽  
Myeloma Proteins ◽  
Group I ◽  
Immune Globulins ◽  
Γ Globulins ◽  
Narrow Bands

Myeloma-like immune globulins present themselves as narrow bands upon paper electrophoresis, and usually show a characteristic appearance in immunoelectrophoresis. Two antigenically different groups of myeloma proteins have been described: groups I and II. Recently, 60% of normal γ-globulin, throughout the mobility range of γ-globulin, has been shown to possess the antigen characteristic for group I, and 30% that for group II myeloma. Occurrence of myeloma-like proteins in the serum is not restricted to multiple myeloma. They may also be seen with other tumors, such as reticulum cell sarcoma, and various carcinomas. In addition, Sonnet and Milhaux have reported on the frequent occurrence of myeloma-like ("monoclonal") γ-globulins in the serum of adult Bantus with different diseases. When large amounts of a myeloma protein are present in the serum, it may be found in a much lower concentration in the spinal fluid.

scholarly journals NATURALLY OCCURRING HUMAN ANTIBODY REACTING WITH BENCE JONES PROTEINS

1964 ◽  
Vol 120 (5) ◽  
pp. 733-745 ◽  
Author(s):  
Wallace V. Epstein ◽  
Dale Gross
Keyword(s):  
Human Antibody ◽  
Bence Jones Protein ◽  
Covalent Bonds ◽  
Naturally Occurring ◽  
Human Sera ◽  
Normal Human ◽  
Group 2 ◽  
Polypeptide Chains ◽  
Individual Human ◽  
Bence Jones Proteins

Agglutinating substances having characteristics of naturally occurring macroglobulin antibodies to human Bence Jones proteins have been identified in human sera. By means of hemagglutination and hemagglutination inhibition techniques, common determinants have been demonstrated on the light (L) polypeptide chains of pooled normal human γ2-globulin and on some Bence Jones proteins of group 1 but not of group 2. Individual human sera serve to delineate subgroups of the two major antigenic groups of the Bence Jones proteins by agglutinating cells coated by one but not another protein of the same antigenic group. The complexity of subgroups, especially of group 2, is established by testing a panel of Bence Jones proteins of the same group for their ability to inhibit hemagglutination. By this means it appeared that different sera recognized different group-specific determinants of cells coated with a single Bence Jones protein. The capacity of the L polypeptide chains and proteolytic fragments of γ2-globulin to inhibit the hemagglutination reaction between Bence Jones protein or L chain-coated cells and human sera was examined. These studies demonstrated that the determinants, toward which agglutinators of human serum are directed, appear to be blocked in intact γ2-globulin and in all fragments in which H chain remains in proximity to L chain. It would appear that the presence of H chains bound to L chains by non-covalent bonds completely obstructs the reactivity of the involved L chain groups. The agglutinating capacity of a serum toward Bence Jones proteins or L chains of γ2-globulin appeared to be independent of its agglutinating capacity for cells coated with intact γ2-globulin. No correlation of the presence in serum of agglutinators for Bence Jones proteins or L chains with health or disease has been established.

scholarly journals CLASSIFICATION OF MYELOMA PROTEINS, BENCE JONES PROTEINS, AND MACROGLOBULINS INTO TWO GROUPS ON THE BASIS OF COMMON ANTIGENIC CHARACTERS

1962 ◽  
Vol 116 (6) ◽  
pp. 859-877 ◽  
Author(s):  
Mart Mannik ◽  
Henry G. Kunkel
Keyword(s):  
Multiple Myeloma ◽  
Antigenic Determinants ◽  
General Category ◽  
Myeloma Protein ◽  
Myeloma Proteins ◽  
Protein Molecules ◽  
Bence Jones Proteins

Antisera to normal 7S γ-globulin and to Bence Jones proteins permit the grouping of myeloma proteins (gamma and beta 2A types), Bence Jones proteins, and the Waldenström type macroglobulins into two fundamental antigenic groups. The antigenic determinants responsible for this grouping are common to all these proteins which fall in the general category of immunoglobulins. Antisera to Bence Jones proteins were particularly useful for this classification since they failed to react with the proteins of the opposite group. These antisera also permit the grouping of normal 7S γ-globulin into two major types. The Bence Jones proteins from individual patients were found to correspond in antigenic group to that of the serum myeloma protein. Studies with antisera to 7S γ-globulin and to Bence Jones proteins indicated that the Bence Jones proteins were antigenically identical to a portion of the corresponding multiple myeloma protein molecules.

The conformation of an atypical IgG myeloma protein and its papain fragments

1970 ◽  
Vol 48 (7) ◽  
pp. 784-789 ◽  
Author(s):  
G. E. Connell ◽  
K. J. Dorrington ◽  
A. F. Lewis ◽  
D. M. Parr
Keyword(s):  
Molecular Weight ◽  
The Other ◽  
Optical Rotatory Dispersion ◽  
Rotatory Dispersion ◽  
Optical Rotatory ◽  
Fab Fragment ◽  
Myeloma Protein ◽  
Myeloma Proteins ◽  
Parent Protein ◽  
Polypeptide Chains

An immunoglobulin IgG (Sackfield) which is known to have polypeptide chains shorter than those of typical proteins of its class has been subjected to fragmentation by papain in the presence of cysteine. One fragment was recovered which was indistinguishable from normal Fc fragment. The other fragment was related to normal Fab fragment but differed from it in several of its properties. The molecular weight was only one-half that of normal Fab. The optical rotatory dispersion spectrum of IgG (Sackfield) had features which differed from those of typical IgG myeloma proteins. The optical rotatory dispersion spectrum of Fc (Sackfield) was identical with those of other myeloma proteins, while the Fab (Sackfield) spectrum reflected the differences observed in the parent protein.

scholarly journals GENETIC CHARACTERS OF HUMAN γ-GLOBULINS IN MYELOMA PROTEINS

1962 ◽  
Vol 116 (5) ◽  
pp. 719-738 ◽  
Author(s):  
M. Harboe ◽  
C. K. Osterland ◽  
M. Mannik ◽  
H. G. Kunkel
Keyword(s):  
Plasma Cells ◽  
Protein Product ◽  
Myeloma Protein ◽  
Myeloma Proteins ◽  
Normal Individuals ◽  
Γ Globulins ◽  
Normal Human ◽  
Genetic Characters ◽  
Single Plasma ◽  
Bence Jones Proteins

The genetic factors Gm(a), Gm(b), Gm(x), and Inv(a), Inv(b) described for normal human γ-globulin were all found in different myeloma proteins. A single myeloma protein never contained more than one product of alternate alleles even in heterozygous individuals. However, factors determined by the two different loci were often found in the same myeloma protein. The Gm(a) character of the myeloma protein parallelled that of the normal γ-globulin of the same serum in most cases. In contrast, the Gm(b) character was usually absent in the myeloma protein when it was directly demonstrable in the normal γ-globulin. The myeloma proteins from six Negroes were Gm(a+b-), whereas the normal γ-globulin was Gm(a+b+). This indicates that the effect of gene Gmb is similar in Negroes and whites, even though its relation to gene Gma is different in the two races. Gm factors were found only in the 7S γ-globulin type myelomas and not in other products of plasma cell tumors. Inv characters were, however, present in all four types of proteins studied, namely 7S and 19S γ-globulins, ß2A-globulins, and Bence Jones proteins. In two instances, genetic heterogeneity of the protein products was demonstrated suggesting the proliferation of more than one clone of plasma cells in some multiple myeloma patients. The accumulated evidence obtained in this study strongly suggested that the presence and absence of genetic characters was compatible with the concept that myeloma proteins were closely analogous to individual moieties in the spectrum of normal γ-globulins rather than truly abnormal proteins. Their study offered evidence of a heterogeneity of genetic characters among the normal γ-globulins in a given individual. It also appears probable that in normal individuals single plasma cells have a restricted capacity to express genetic information in their protein product.

Sign in / Sign up

Export Citation Format

Share Document