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 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 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 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.

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 SYNTHESIS AND ASSEMBLY OF IMMUNOGLOBULINS BY MALIGNANT HUMAN PLASMACYTES

1970 ◽  
Vol 132 (1) ◽  
pp. 148-162 ◽  
Author(s):  
Susan Zolla ◽  
Joel Buxbaum ◽  
E. C. Franklin ◽  
M. D. Scharff
Keyword(s):  
Plasma Cells ◽  
Cellular Level ◽  
Urinary Proteins ◽  
Myeloma Protein ◽  
Bence Jones Proteins

Three basic patterns of γ-globulin synthesis are described in malignant human plasmacytes: extreme unbalanced synthesis where only L chains are synthesized; unbalanced synthesis in which intact γG globulin and an excess of free L chains are synthesized and secreted; and balanced synthesis where H and L chains appear to be synthesized in equimolar amounts. Studies of the cellular products appear to reflect the biosynthetic processes of the cells in a more reliable fashion than does analysis of serum or urinary proteins. The absence of Bence Jones proteins from the urine does not necessarily indicate that free L chains are not being synthesized and secreted at the cellular level. Similarly, the completed globulin molecule secreted by malignant plasma cells may not be demonstrable by examination of serum. Patterns of globulin synthesis in human myelomatous tissues vary as do patterns of globulin synthesis in mouse plasmacytomas. Pulse-chase studies of the cells from one patient showed that a γG myeloma protein was assembled via an HL (half molecule) intermediate.

scholarly journals ANTIGENIC RELATIONSHIPS BETWEEN IMMUNE GLOBULINS AND CERTAIN RELATED PARAPROTEINS IN MAN

1961 ◽  
Vol 114 (4) ◽  
pp. 521-533 ◽  
Author(s):  
Edward C. Franklin ◽  
Denis R. Stanworth
Keyword(s):  
Biological Properties ◽  
The Other ◽  
Antigenic Specificity ◽  
Myeloma Proteins ◽  
Antigenic Properties ◽  
Immune Globulins ◽  
Γ Globulins ◽  
Antigenic Relationships ◽  
Gel Diffusion ◽  
Bence Jones Proteins

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.

scholarly journals Inhibition of Factor XI by Myeloma Protein M.

1977 ◽  
Author(s):  
A. Rimon ◽  
I. Raz ◽  
M. Lahav
Keyword(s):  
Coagulation Factor ◽  
Coagulation Factors ◽  
Normal Human Plasma ◽  
Clotting Factors ◽  
Factor Xi ◽  
Myeloma Protein ◽  
Myeloma Proteins ◽  
Normal Human ◽  
Time Test ◽  
Hemostatic Disorders

Waldenstrom’s macroglobulinemia sometimes involves hemostatic disorders. It has been assumed that this may be due to interaction of the myeloma protein with soom blood coagulation factor(s). In the present investigation the sera of seven myeloma patients were studied for a possible interaction between the myeloma protein and clotting factors II, VIM, IX and XI.Normal human plasma was incubated for 30 mi η at 37°C with different dilutions of patients’ serum or of purified myeloma proteins. The ability of this mixture to restore the clotting times of various deficient plasmas was tested by the partial thromboplastin time test.Factor XI activity of normal plasma was substantially inhibited upon incubation with patient’s serum or with purified myeloma protein M. This effect seems to be specific for myeloma protein M since it was neither observed with myeloma proteins G or A, nor with normal IgM. Other coagulation factors investigated so far were not inhibited by myeloma protein M. It is concluded that this protein is specifically affine to factor XI resulting in hindering the latter’s activity.

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 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 THE SITE OF SYNTHESIS OF THE 19S γ-GLOBULINS IN DYSGAMMAGLOBULINEMIA

1962 ◽  
Vol 115 (6) ◽  
pp. 1141-1148 ◽  
Author(s):  
Andre Cruchaud ◽  
Fred S. Rosen ◽  
John M. Craig ◽  
Charles A. Janeway ◽  
David Gitlin
Keyword(s):  
Plasma Cells ◽  
Normal Subjects ◽  
High Serum ◽  
Splenic Tissue ◽  
Methyl Green ◽  
Serum Concentrations ◽  
Normal Individuals ◽  
Γ Globulins ◽  
Transitional Cells ◽  
Marked Deficit

Lymph nodes and splenic tissue from patients with congenital agammaglobulinemia and dysgammaglobulinemia and from normal subjects were studied with the use of immunofluorescence and histochemical stains to determine the site of synthesis of the 19S γ1-globulins. The two patients with dysgammaglobulinemia had high serum concentrations of the 19S γ1-globulins and a marked deficit of the 7S γ-globulins. These patients, as well as agammaglobulinemic children, had only rare or no plasma cells in their tissues. Cells were identified in sections of spleen from a dysgammaglobulinemic child as well as from normal individuals which exhibited specific fluorescence with an anti-19S γ-globulin antiserum adsorbed with 7S γ2-globulins and which stained positively with PAS and methyl green pyronine. These cells resembled the transitional cells described by Fagraeus.

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