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.

scholarly journals TWO MAJOR TYPES OF NORMAL 7S γ-GLOBULIN

1963 ◽  
Vol 117 (2) ◽  
pp. 213-230 ◽  
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.

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 DISTRIBUTION AMONG THE γ-GLOBULIN MOLECULES OF DIFFERENT GENETICALLY DETERMINED ANTIGENIC SPECIFICITIES IN THE GM SYSTEM

1965 ◽  
Vol 122 (4) ◽  
pp. 799-811 ◽  
Author(s):  
Lars Mårtensson ◽  
Henry G. Kunkel
Keyword(s):  
Genetic Factors ◽  
Polypeptide Chain ◽  
Antigenic Determinants ◽  
Racial Groups ◽  
Myeloma Protein ◽  
Myeloma Proteins ◽  
Chain Group ◽  
The Common ◽  
Genetically Determined

Isolated myeloma proteins and anti-Rh antibodies were utilized for determination of the distribution among the γ-globulin molecules of various Gm(b) and Gm(f) determinants. All of these genetic factors are as a rule inherited together in Caucasians, but not in other races. The Gm(b) determinants, except (b2), were found together in the same Caucasian myeloma globulins of the Vi H chain group, which never carried Gm(f) or (b2). The Gm(f) and (b2) determinants were found together in other myeloma globulins, of the We group. Anti-Rh antibody molecules appeared to be similar to myeloma molecules in these respects. A few myeloma proteins and anti-Rh antibodies were encountered which reacted with some but not other anti-Gm(b) or anti-Gm(f) reagents; the only available Vi type myeloma protein from a Negro, specifically lacked the Gm(b3) factor. The observations might be explained by the following hypothesis: In Caucasians with the common Gmf Gmb gene complex the Gm(b) antigenic determinants, except (b2), co-occur in certain molecules, which contain a polypeptide chain determined by the Gmb gene; the Gm(f) and (b2) determinants co-occur in other molecules, which contain a polypeptide chain determined by the Gmf gene. Individuals that lack some Gm(b) or Gm(f) determinants most likely have a gene partly different from Gmb or Gmf. The value of studies with myeloma proteins from individuals of different racial groups was apparent from this study. One myeloma protein from a Chinese was unique in that it was both Gm(a+) and Gm(f+).

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.

scholarly journals Brief Report: Two Bence Jones Proteins of Different Immunologic Types in the Same Patient with Multiple Myeloma

Blood ◽  
1966 ◽  
Vol 27 (1) ◽  
pp. 74-77 ◽  
Author(s):  
RALPH L. ENGLE ◽  
RALPH L. NACHMAN
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
The Other ◽  
Myeloma Protein ◽  
Type K ◽  
Bence Jones Proteins

Abstract In summary, two Bence Jones proteins, one of type K and the other of type L immunologic specificity, and a serum myeloma protein of type L were demonstrated in the same patient with multiple myeloma. It is probable that, in this instance, dissemination from at least two clones of plasma cells has occurred.

scholarly journals INDIVIDUAL ANTIGENIC SPECIFICITY OF MYELOMA PROTEINS

1965 ◽  
Vol 121 (4) ◽  
pp. 561-575 ◽  
Author(s):  
Howard M. Grey ◽  
Mart Mannik ◽  
Henry G. Kunkel
Keyword(s):  
Antigenic Specificity ◽  
Antigenic Structure ◽  
Light Chains ◽  
Antigenic Determinants ◽  
Fab Fragment ◽  
Myeloma Protein ◽  
Heavy Chains ◽  
Myeloma Proteins ◽  
The Individual ◽  
Individual Specificity

The specific antigenic structure of individual myeloma proteins was investigated for the presence of similar antigenic determinants in pooled γ-globulin and for the localization of these determinants on the γ-globulin molecules. Quantitative precipitin analyses demonstrated that in most instances absorption of antisera specific for an individual myeloma protein with large amounts of γ-globulin markedly reduced or completely removed the reactivity of the antiserum for the homologous myeloma protein. In only one instance did strong specificity remain after absorption with 100 mg of Fr II per cc of antiserum. The antigenic determinants responsible for the individual specificity were localized in all cases studied solely to the Fab fragment produced by papain digestion. After reductive cleavage, three patterns of localization were observed. Individual specificity could be localized either to; (a) isolated heavy chains, (b) isolated light chains, (c) antigenic determinants present only when light and heavy chains were recombined. After immunization with whole myeloma proteins, individual specificity was localized in part at least to the isolated heavy chain in four of six proteins studied. It was localized to the light chains in three of five type L proteins but in none of six type K proteins. In the instances where individual specificity of the myeloma protein was present on the light chains, it was shown that the Bence Jones protein from the same patient also contained the individual specificity. Immunization with isolated heavy or light chains furnished further evidence for the individual specificity of both types of chains. These studies on myeloma proteins furnished evidence concerning the portions of the γ-globulin molecule subject to individual antigenic variation. The light chains, particularly the L type and the Fd portion of the heavy chains were primarily involved. Evidence for the importance of the quaternary structure was also obtained from the necessity in some instances for light and heavy chains to be associated in order for individual specificity to be observed. The Fc fragment of the heavy chains on the other hand showed very limited variation which was related to subgroup specificity.

scholarly journals ENZYMATICALLY PRODUCED SUBUNITS OF PROTEINS FORMED BY PLASMA CELLS IN MICE

1962 ◽  
Vol 115 (3) ◽  
pp. 641-653 ◽  
Author(s):  
Brigitte A. Askonas ◽  
J. L. Fahey
Keyword(s):  
Plasma Cells ◽  
Deae Cellulose ◽  
Cell Tumor ◽  
Antigenic Determinants ◽  
Bence Jones Protein ◽  
Myeloma Protein ◽  
Myeloma Proteins ◽  
Γ Globulins ◽  
Relationship Of ◽  
The Relationship

The relationship of Bence Jones protein (mol wt = 45,000) to a ß2A-myeloma protein (mol wt = 160,000) formed by the same mouse plasma cell tumor (MPC-2) was investigated. The ß2A-myeloma protein was split by treatment with papain and cysteine into fragments (S20,w = 3.7S), similar in size to the Bence Jones protein (S20,w = 3.6S). Two types of fragments with distinct antigenic groupings designated S and F, were present in the MPC-2 myeloma protein digest. These were partially separated by DEAE-cellulose chromatography. The Bence Jones protein was found to share antigenic determinants with S fragments from the MPC-2 ß2A-myeloma protein and with S fragments from γ-globulins. Physicochemical observations indicated, however, that the Bence Jones protein was not identical to the globulin fragments produced by treatment with papain and cysteine. Comparison of the S and F fragments from ß2A- and γ-globulins revealed that the antigenic features shared by the various globulins derived from plasma cells (γ- and ß2A-myeloma proteins, the range of normal γ-globulins) are largely properties of the S fragments, whereas the distinctive antigenic differences between the γ- and ß2A-myeloma proteins were properties which appeared in the F fragments of the molecules.

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.

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

Blood ◽  
1963 ◽  
Vol 21 (4) ◽  
pp. 403-423 ◽  
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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