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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Normal adult BALB/c mice are virtually unresponsive to the idiotype of myeloma protein T15 when immunized with purified T15. However, antibodies to the T15 idiotype can be elicited by T15 in BALB/c mice that are reared in a germ-free environment or injected as newborns with an alloantiserum to the idiotype. Some germ-free and neonatally suppressed mice also produce helper cells (presumably T helpers) that enhance B-cell production of anti-DNP antibodies in response to DNP-T15. Taken together with previous studies, the present results mean that so far there are no exceptions to the rule that BALB/c mice have B and T cells that can respond to idiotypes of myeloma proteins of BALB/c origin. There appears to be a reciprocal relation between the natural prevalence of an immunoglobulin's idiotype and its immunogenicity in isologous individuals. The findings support proposals for an immune network of idiotypes and anti-idiotypes. Besides binding one or more extrinsic antigens, it is likely that each immunoglobulin also binds the idiotype of some other immunoglobulin. An immune network therefore implies multispecificity of antibodies.
Cold Spring Harb Symp Quant Biol 1977
PMID:Immune responses of BALB/c mice to the idiotype of T15 and of other myeloma proteins of BALB/c origin: implications for an immune network and antibody multispecificity. 7 Mar 7

1. A series of Dnp (dinitrophenyl) nitroxide spin labels was used to map the dimensions of the combining site of the Dnp-binding immunoglobulin A myeloma protein MOPC 315. The method compares the observed e.s.r. (electron-spin-resonance) hyperfine splittings with those calculated on the basis of different postulated motions for the spin label. The analysis is complicated by the sensitivity of the e.s.r. hyperfine splitting to the overall ;tumbling' time of the antibody-hapten complex and the polarity of the spin-label's environment. When these effects are considered quantitatively, it is then possible to determine the degree of mobility of each hapten which is allowed by the shape of the combining site. 2. The dinitrophenyl ring is rigidly held, and the depth of the site is 1.1-1.2nm and has lateral dimensions at the entrance to the site >/=0.6nmx0.9nm. The analysis of the results for spin-labelled haptens with chiral centres allows these lateral dimensions to be refined to 0.8nm and 1.1nm, and it is shown that the site is asymmetric with respect to the plane of the dinitrophenyl ring. 3. A polarity profile of the combining site was also obtained and a positively charged amino acid residue, possibly arginine-95(L) (light chain), was located at the entrance to the site. 4. The binding of Gd(III) to the antibody-hapten complexes results in quenching of the e.s.r. signal of the nitroxide. By using La(III) as a control, the paramagnetic contribution to the quenching is measured. 5. Analysis of the differential quenchings of the enantiomers of two five-membered nitroxide ring spin labels gives two possible locations of the metal-binding site. One of these is equidistant (0.7nm) from each of the three dinitrophenyl aromatic protons, and nuclear-magnetic-resonance relaxation studies, at 270MHz, on solutions of dinitrobenzene, Gd(III) and the Fv fragment (variable region of heavy and light chain) from protein MOPC 315 support this location for the metal site. 6. The e.s.r. and metal-binding data were then compared with the results of a model of the combining site constructed on the basis of framework invariance in immunoglobulins [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol.41, in the press]. The overall agreement is very good. Assignments of possible chelating groups for the metal can be made.
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PMID:The gross architecture of an antibody-combining site as determined by spin-label mapping. 20 Feb 19

Several K immunoglobulin antisera out of a large number studied showed the unique property of reacting with a membrane structure present on all T and B lymphocytes examined. This antigen was detected on lymphocytes by indirect fluorescence, direct fluorescence, and by cytotoxic analysis. Absorption of the antiserum by all K myeloma proteins, K Bence-Jones proteins, and kappa light chains removed the activity; L proteins had no effect. The possibility that the cross-reacting membrane antigen is part of the HL-A system was discussed.
Cold Spring Harb Symp Quant Biol 1977
PMID:An unusual kappa immunoglobulin antigen present on the membrane of T and B lymphocytes. 40 95

The VH specificities of two rabbit antisera raised against the H chains of two human IgM cold agglutinins were studied with the aid of proteins on which the VH sequence data are available. They were found to recognize a new VH antigen (VHMar), which may represent a subgroup of VHI. This antigen is found on anti-Ii antibodies which have cross-reactive idiotypes. It is moderately well-expressed in normal gamma globulin and strongly expressed on 8% of unselected myeloma and macroglobulinaemia proteins. There is evidence to suggest that a proportion of the cross-reactive idiotypes among the anti-Ii antibodies involve this VH antigen.
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PMID:An immunoglobulin heavy chain variable region (VH) marker associated with cross-reactive idiotypes in man. 41 66

We have investigated the organization of immunoglobulin genes in mice. High molecular weight DNA from myelomas and Krebs ascites cells was cleaved with EcoRI restriction endonuclease and fractionated using preparative agarose gel electrophoresis. Each fraction was then hybridized to an immunoglobulin mRNA or a cDNA transcribed from the mRNA. In two series of experiments, one with a kappa chain probe (MOPC 41 mRNA), the other with a lambda chain probe (SAPC 178 mRNA), we analyzed a variety of myeloma DNAs and Krebs DNA. In contrast to previously reported findings (Tonegawa, S., et al. (1976) Cold Spring Harbor Symp. Quant. Biol. 41, 877), we did not observe any unique restriction map pattern in the DNA from cells which exress a given immunoglobulin gene. We also found that restriction fragments containing c region genes do not appear to transpose, while DNA sequences corresponding to other portions of the kappa and lambda mRNAs do in some cases.
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PMID:Immunoglobulin genes in DNA restriction fragments. 69 88

Magnetic-resonance techniques are used to refine the model of the combining site of the Fv fragment of the dinitrophenyl-binding mouse myeloma protein MOPC 315 constructed by Padlan, Davies, Pecht, Givol & Wright (1976) (Cold Spring Harbor Symp. Quant. Biol.41, in the press). Light-absorption studies indicate a dinitrophenyl-tryptophan interaction in the Fv fragment of the type occurring in free solution. The Dnp-aspartate-tryptophan complex is therefore used as a starting point for the n.m.r. (nuclear-magnetic-resonance) analysis of the dinitrophenyl-Fv fragment interaction. Ring-current calculations are used to determine the geometry of the complex. The specificity of complex-formation between dinitrophenyl and tryptophan is confirmed by the lack of ring-current shifts of the dinitrophenyl resonances when tryptophan is replaced by any other aromatic amino acid. Proton n.m.r. difference spectra (at 270MHz), resulting from the addition of a variety of haptens to the Fv fragment, show that the combining site is highly aromatic in nature. Calculations on the basis of ring-current shifts define the geometry of the combining site, which involves a dinitrophenyl ring in van der Waals contact with four aromatic amino acid residues on the protein. The observation of a nuclear Overhauser effect on the H((3)) resonance of the dinitrophenyl ring provides additional constraints on the relative geometry of the H((3)) proton and an aromatic amino acid residue on the Fv fragment. The specificity of the Fv fragment for dinitrophenyl ligands arises from a stacking interaction of the dinitrophenyl ring with tryptophan-93(L), in an ;aromatic box' of essentially tryptophan-93(L), phenylalanine-34(H) and tyrosine-34(L); asparagine-36(L) and tyrosine-34(L) also contribute by forming hydrogen bonds with the nitro groups on the dinitrophenyl ring. The n.m.r. results also confirm that the antibody-hapten reaction may be visualized as a single encounter step. An Appendix shows the method of calculation of ring currents for the four aromatic amino acids and their use in calculating structures.
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PMID:The combining site of the dinitrophenyl-binding immunoglobulin A myeloma protein MOPC 315. 92 44

The pKa values of the three histidine residues in the Fv fragment (variable region of the heavy and light chains) of the mouse myeloma protein MOPC 315, measured by high resolution n.m.r. (nuclear magnetic resonance), are 5.9, 6.9 and 8.2. The perturbation of the pKa of one of the histidines (pKa 6.9) on the addition of hapten and the narrow linewidth of its proton resonances suggests that it is at the edge of the combining site. References to the model of the Fv fragment [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol. 41, in the press] allows assignment of the three histidine residues, histidine-102H, histidine-97L and histidine-44L. The determination of the pKa of the phosphorus group, by 31P n.m.r., of a homologous series of Dnp- and Tnp- (di- and tri-nitrophenyl) haptens has located a positively charged residue. Molecular-model studies on the conformations of these haptens show that the residue is at the edge of the site. The model suggests that the positively charged residue is either arginine-95L or lysine-52H.
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PMID:Specificity of interactions of hapten side chains with the combining site of the myeloma protein MOPC 315. 92 46

A 45-year-old man developed in 1965 skin lesions on cold exposure and was found to have cryoglobulinemia due to an M-component of IgG class. Glomerular damage was first noted in 1970, and progressed to renal impairment and nephrotic syndrome during the next two years. Reduced serum levels of complement components C3 and C4 were found, indicating in vivo complement activation. Renal biopsy revealed proliferative glomerulonephritis and deposition of IgG and C3 along the glomerular basement membrane. Electron microscopical examination revealed a striking deposition of a 'fibrillar' or microcrystalline material in the glomerular basement membrane. This material had an ultrastructure similar to that found in the cryoprecipitate from serum. There were no tubular changes of myeloma type, neither were there any monoclonal light chains detected in the urine. So far, there are no other signs of myeloma or lymphoma. Immunosuppressive treatment with prednisone and cyclophosphamide resulted in a decrease in the serum M-component as well as a decrease in protein leakage through the glomeruli and a return to normal of glomerular filtration rate. The finding of monoclonal cryoglobulinemia, demonstrable at room temperature, in a patient developing proliferative glomerulonephritis with complement activation is unusual. It is probably that the M-component is causally related to the glomerular lesions.
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PMID:Monoclonal IgG cryoglobulinemia with secondary development of glomerulonephritis and nephrotic syndrome. 117 19

Normal human pooled plasma was fractionated by a variety of methods. The IgE concentration of the different fractions was determined by a solid-phase radioimmunoassay. The results of these studies indicate, that polyclonal IgE behaves similarly to IgE of myeloma origin. A biospecific method was worked out to purify IgE from fraction III of the cold ethanol fractionation procedure.
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PMID:Behaviour of polyclonal human IgE in the course of fractionation. 123 46

A 40-year-old woman had cryocrystalglobulinemia with IgG2(K1). To date, 27 other cases of spontaneous crystallization of a plasma protein have been reported. In all, the protein, a cryoglobulin, has been found to be an IgG molecule. The disease most commonly associated with this phenomenon has been multiple myeloma. None of the patients have had Raynaud's phenomenon, but many have had purpuric skin lesions made worse by exposure to cold. In the two cases of essential cryocrystalglobulinemia, crystals were found in the peripheral blood film. Immunologic, biochemical and ultrastructural studies have so far not demonstrated any property common to all cryocrystalglobulins.
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PMID:Cryocrystalglobulinemia. 126 77


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