Solomon A, Fahey JL, Malmgren RA. Immunohistologic localization of gamma-1-macroglobulins, beta-2A-myeloma proteins, 6.6 S gamma-myeloma proteins and Bence Jones proteins. Blood. 1963;21(4):403-423.

The antigenic properties of normal 19S γ-globulin, pathologic macroglobulins, ß2A-myeloma proteins, and Bence Jones proteins have been compared with 7S γ-globulin and the small 3.5S units derived from it by gel diffusion precipitin techniques. These studies demonstrate that the determinant groups on the 7S γ-globulin molecule responsible for the cross-reaction with each of the other proteins are associated with the two fragments of 7S γ-globulin which have the antibody-combining sites. The antigenic specificity of the 7S γ-globulin which distinguishes it from each of these proteins is associated primarily with the fragment that is richest in hexose and can not combine with antigen. However when compared with certain of the paraproteins additional antigenic specificity was also found to reside in the fragments with antibody-combining activity. The finding of similar antigenic relationships in rabbit γ-globulins suggests that some of the biological properties associated only with the 7S γ-globulins and not with the other immune globulins may reside in the fragment which also carries the antigenic specificity of the protein.

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

Journal of Experimental Medicine ◽

10.1084/jem.116.6.859 ◽

1962 ◽

Vol 116 (6) ◽

pp. 859-877 ◽

Cited By ~ 82

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.

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

Journal of Experimental Medicine ◽

10.1084/jem.118.1.41 ◽

1963 ◽

Vol 118 (1) ◽

pp. 41-53 ◽

Cited By ~ 39

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.

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GENETIC CHARACTERS OF HUMAN γ-GLOBULINS IN MYELOMA PROTEINS

Journal of Experimental Medicine ◽

10.1084/jem.116.5.719 ◽

1962 ◽

Vol 116 (5) ◽

pp. 719-738 ◽

Cited By ~ 71

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.

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BENCE JONES PROTEINS AND LIGHT CHAINS OF IMMUNOGLOBULINS

Journal of Experimental Medicine ◽

10.1084/jem.130.6.1295 ◽

1969 ◽

Vol 130 (6) ◽

pp. 1295-1311 ◽

Cited By ~ 29

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.

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

Journal of Experimental Medicine ◽

10.1084/jem.119.5.817 ◽

1964 ◽

Vol 119 (5) ◽

pp. 817-836 ◽

Cited By ~ 55

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.

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Immunohistologic Localization of Gamma-1-Macroglobulins, Beta-2A-Myeloma Proteins, 6.6 S Gamma-Myeloma Proteins and Bence Jones Proteins

Blood ◽

10.1182/blood.v21.4.403.403 ◽

1963 ◽

Vol 21 (4) ◽

pp. 403-423 ◽

Cited By ~ 63

Author(s):

ALAN SOLOMON ◽

JOHN L. FAHEY ◽

RICHARD A. MALMGREN

Keyword(s):

Cellular Localization ◽

Indirect Evidence ◽

Malignant Cell ◽

Specific Protein ◽

Lymphoid Cells ◽

Malignant Cells ◽

Serum Globulin ◽

Myeloma Protein ◽

Myeloma Proteins ◽

Bence Jones Proteins

Abstract The cellular localization of 6.6 S γ-globulins, β2A-globulins, γ1-macroglobulins and Bence Jones proteins was studied by immunohistochemical procedures in 21 patients with multiple myeloma or macroglobulinemia. Each type of protein was identified by specific immunofluorescence in a variety of morphologic forms of malignant cells. Some cells were typically plasmacytic, some were lymphoid cells and others were immature forms. It was clear that γ, β2A, γ1M, and Bence Jones proteins were not associated exclusively with a single morphologic form of malignant cell. The variety of immunofluorescent positive cells in each patient was more restricted, however, than in a group of patients with a specific protein abnormality. In patients with anomalous proteins, all or almost all of the malignant cells were found to contain the specific anomalous protein. The malignant cells contained either γ-myeloma protein, β2A-myeloma protein or γ1-macroglobulin in patients with these types of anomalous protein. Only one class of globulin was found in individual cells. In patients with Bence Jones proteins as the sole anomalous protein, all the malignant cells appeared to have Bence Jones protein. Where an anomalous serum globulin coexisted with Bence Jones proteins, indirect evidence indicated that the Bence Jones proteins and the larger globulin were formed in the same cells.

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TWO MAJOR TYPES OF NORMAL 7S γ-GLOBULIN

Journal of Experimental Medicine ◽

10.1084/jem.117.2.213 ◽

1963 ◽

Vol 117 (2) ◽

pp. 213-230 ◽

Cited By ~ 77

Author(s):

Mart Mannik ◽

Henry G. Kunkel

Keyword(s):

Multiple Myeloma ◽

Antigenic Determinants ◽

Myeloma Proteins ◽

Group 2 ◽

Group 1 ◽

Bence Jones Proteins

Normal 7S human γ-globulin was found to contain two fundamental antigenic groups of molecules. The group 1 molecules of normal γglobulin correspond antigenically to group 1 multiple myeloma proteins and Bence Jones proteins; and group 2 molecules of normal γ-globulin correspond antigenically to group 2 multiple myeloma proteins and Bence-Jones proteins. Among pooled human Fr II and several individual γ-globulin preparations, approximately 60 per cent of molecules belong to group 1 and approximately 30 per cent of molecules to group 2 in this classification. The possible existence of a third minor antigenic group, constituting about 10 per cent, is discussed. Antisera to Bence Jones proteins of antigenic group 1 and group 2, in conjunction with I-131-labeled 7S γ-globulin proved to be the most useful system for defining the antigenic groups of normal γ-globulin. The group-specific antigenic determinants of normal 7S γ-globulin molecules were located on the S fragments of these proteins.

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