Immunogenicity and antigenicity of immunoglobulins. XII. Intact light chain and heavy chain isotype-restricted Vk-associated epitopes.
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Immunization with intact IgG has allowed the isolation of four hybridomas producing antibodies recognizing epitopes expressed within subpopulations of human kappa light chains unrelated to known polymorphisms (Km) and previously defined V-region subgroups. The V-region-associated epitopes recognized are conformation-dependent, being expressed on intact light chain but not on isolated VK or CK fragments. The frequency of expression within paraprotein panels of different heavy chain isotypes varied between individual antibodies. An epitope recognized by B2A6, expressed by greater than 85% IgGK paraproteins, was not represented in 16 IgM paraproteins tested, suggesting that association of VK with mu chains does not result in display of the epitope recognized, or alternatively, that selective association between VK and CH gene products occurs. These data contrast with the reactivity of other McAb for CK epitopes which were reactive with isolated CK fragments, and for all kappa-bearing paraproteins, regardless of heavy chain isotypes. (+info)
Immunogenic and antigenic epitopes of immunoglobulins. XVIII. Subpopulations of human lambda chains defined with a panel of monoclonal antibodies.
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Following immunization with various lambda Bence-Jones proteins, over 100 hybridomas were established. A majority of the monoclonal antibodies (McAb) produced were demonstrated to recognize epitopes common to all lambda chains or unique to the immunogen. Twenty-nine McAb exhibited profiles of 'restricted' reactivity. Analysis with a panel of serologically defined antigens allowed McAb recognizing the lambda II subgroup to be identified. Other McAb recognized epitopes selectively expressed by lambda II and lambda III subgroup proteins. A further twenty-one McAb exhibited individual specificity profiles, some of which detect minor lambda chain subpopulations. Several of these McAb have potential for analysis of the clonality of specific antibody responses and for detecting monoclonal B-cell proliferations. (+info)
A simple silver-staining technique for detecting Bence Jones proteins in unconcentrated urine.
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Detection of Bence Jones proteins in urine usually involves a concentration step, followed by electrophoresis and, if necessary, immunofixation. The time-consuming and expensive concentration step can be eliminated by use of the silver-stain technique described here. This procedure, routinely used for staining unconcentrated urine, is inexpensive, sensitive, and easily performed in a clinical laboratory. Bence Jones proteins can be detected in concentrations as low as 5 mg/L. (+info)
Studies of a human lambda-chain epitope related to a complementarity-determining region.
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A tryptic non-adecapeptide representing the 24-42 sequence of the MCG lambda-type Bence-Jones protein, and which contains its entire complementarity-determining region-1, was isolated. The peptide was utilized in preparing an affinity column that was used to isolate an antibody having the reactivity of a previously employed idiotypic antibody to MCG. This antibody preparation, as well as 13 monoclonal mouse antibodies to human lambda-chains, was employed in an enzyme-linked immunoassay to detect other Bence-Jones proteins with this serologic specificity. The results obtained with two of the monoclonal antibodies suggest that the epitope in question is a noncontiguous one. (+info)
Renal impairment in myeloma: negative association with isoelectric point of excreted Bence-Jones protein.
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The isoelectric point (pI) of the major form of Bence-Jones protein excreted by 62 patients with myeloma and six with macroglobulinaemia was measured by combining isoelectric focusing with immunoblotting techniques. The distribution of the pI values for both kappa and lambda type proteins was bimodal, most falling in the ranges 5.0-6.0 and 7.0-7.5. Plasma creatinine and creatinine clearance and the urine excretion of alpha-1-microglobulin and beta-2-microglobulin were measured in 24 of the patients. These patients, who were free of additional factors known to have an association with the development of renal impairment, were followed up for a mean period of 16 months (range three to 28 months). It was found that renal impairment was not related to the pI of the Bence-Jones protein excreted. (+info)
Monomer-dimer equilibria of a Bence Jones protein and its variable fragment.
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The circular dichroic (CD) spectra of a type lambda Bence Jones protein (Tod), its variable (VL) fragment, and the constant (CL) fragment of a type lambda protein (Nag) were measured under various conditions. In the pH region from 5.5 to 7.5, the CD spectra of Tod protein with intact interchain disulfide bond (L(SS)) and and CL did not change with pH, while the spectra of Tod protein in which the interchain disulfide bond had been reduced and alkylated (L(RA)) and VL did not change with pH. The dimerization reactions of L(RA) and VL were studied by following the CD change with protein concentration. The CD spectrum of CL did not change with the protein concentration. The dimerization constant for L(RA) was 4 X 10(4) M-1 at at pH 7.5 and 25 degrees C, which was smaller than that for VL (1 X 10(5) M-1). The ellipticity at 278 nm for the L(RA) dimer was different from that for the L(SS) dimer and changed with pH. These findings indicate that the L(RA) dimer and L(SS) dimer have different conformations. The differences in the conformation and L-L interaction between the L(RA) dimer and L(SS) dimer are discussed on the basis of the conformations of VL and CL and the interactions between the paired domains. (+info)
Multiple myeloma with serum IgM kappa and Bence Jones lambda biclonal gammopathy.
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We report a rare finding: IgM kappa and Bence Jones lambda double gammopathy in serum of a 80-year-old man with untreated symptomatic multiple myeloma. The unusual findings are confined to the laboratory studies demonstrating also a Bence Jones lambda proteinuria, high erythrocyte sedimentation rate (113 mm/h), and anemia. The synthesis of the different light chains seems to occur in separate cellular clones. (+info)
Metastatic calcification in the stomach demonstrated by a bone scan in Bence Jones lambda myeloma.
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A 53-year-old male with Bence Jones lambda myeloma developed hypercalcemia and acute renal failure (calcium 14.4 mg/dl, BUN 40 mg/dl, creatinine 3.0 mg/dl) after initial response to chemotherapy. A 99mTc-MDP bone scan revealed unusual isotope accumulation in the left hypochondrium. Extensive calcium deposition was confirmed in the gastric mucosa in the postmortem examination. Detection of gastric calcification by a bone scan is very rare. Only two cases of gastric calcification visualized on bone scans can be found in the literature, one with multiple myeloma) and one in Hodgkin's disease). (+info)