Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The variable domain (V) sequence of the lambda-light chain of the Gar IgG2 human myeloma protein was determined from enzymatically generated peptides that were isolated, characterized, and ordered by overlap and/or by subgroup homology. The sequence consisted of the amino terminal 107 residues of the light chain, and shared subgroup V lambda III-specific residues as well as a pattern of CDR deletions unique to most V lambda III sequences. The structural role of the light V region in the high affinity for flavins and the low affinity for 2,4-dinitrophenyl haptens characteristic of the intact IgG molecule was coarsely assessed by way of model building and by comparison with the refined combining site model of MOPC 315, an Ig with relative affinity values for DNP and riboflavin the converse of those observed in Gar.
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PMID:The modeled structure of the IgG Gar VL region and its implications for anti-flavin and anti-DNP fine specificities. 641 82

Seven BALB/c hybridoma antibodies directed against the protein antigen, hen egg-white lysozyme c (HEL), were characterized on the basis of their ability to bind lysozymes from 10 species of birds, and their ability to bind HEL competitively. The hybridomas were separable into three complementation groups based upon competitive interactions. The fine specificities of all antibodies were distinct, but two, HyHEL-8 and HyHEL-10, had very similar and overlapping reactivity patterns. To test the hypothesis that VL-VH pairing correlates with binding specificity, the N-terminal amino acid sequences were determined to identify the VL and VH isotopes (subgroups) of the anti-HEL antibodies. HyHEL-8 and -10 shared the VK23 light chain isotype and nearly identical heavy chains in Kabat subgroup I, whereas the heavy and light chain isotypes of all other antibodies differed from HyHEL-8 and -10 and from each other. The heavy and light chain isotypes expressed by HyHEL-8 and -10 are also expressed by XRPC-25, a DNP-binding myeloma protein that does not bind lysozyme. These results are discussed with respect to the contributions of various genetic sources of structural diversity to antibody functional diversity.
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PMID:VL-VH expression by monoclonal antibodies recognizing avian lysozyme. 641 16

Cold insolubility of a serum IgA cryoimmunoglobulin was found to be inhibited by the addition of 1.5 mM sodium decanedicarboxylate in vitro. The patient with the cryoglobulin had advanced multiple myeloma complicated by severe hyperviscosity that caused lethargy and episodic loss of consciousness. Decanedicarboxylic acid administered orally resulted in transient relief of symptoms and the loss of cryoprecipitability of the paraprotein. Further in vitro studies revealed that sodium salts of long-chain monocarboxylic acids with a minimum of eight carbons, and dicarboxylic acids with a minimum of 12 carbons inhibited cryoprecipitation. Salts of short-chain carboxylic acids, by contrast, enhanced cryoprecipitation. Sodium phenolate and sodium salts of benzoic acid, 2,4-DNP, phenylpropionic acid, and salicylic acid were also inhibitory. These latter compounds, which have a ring structure, did not cause precipitation at any concentration. It was demonstrated that the presence of a free carboxylic group was required for these activities; conversion of carboxylic acid to amide resulted in the loss of both the inhibitory and cryoprecipitation-enhancing effects. Normal plasma, or plasma from five other patients who had IgG, IgM, or mixed-type cryoglobulinemia, were not affected by any of these compounds. It is suggested that in selected cases of hyperviscosity syndrome associated with cryoglobulinemia, some of these compounds, especially monocarboxylic acids with appropriate chain lengths, or those with a ring structure, may have therapeutic applications.
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PMID:Inhibition of cold insolubility of an IgA cryoglobulin by decanedicarboxylic acid and related compounds. 663 13

The denaturation of IgE immunoglobulin induced by heating at 56 degrees C or by treatment at low pH is inhibited in the presence of high concentrations of salts or hexoses. Between 50 and 100% of the IgE anaphylactic activity (PCA) of rat and mouse antisera is recovered after heating at 56 degrees C for 1,5 or 5 h, respectively, in 1 M MgSO4 or 2 M glucose, mannose or fructose. Anaphylactic activity of IgE monoclonal anti-DNP mouse antibody is equally preserved. The specific antigenic determinants of human and rat IgE myeloma proteins are also thermostable in these conditions. The addition of MgSO4 or glucose protects IgE anaphylactic antibodies against denaturation at pH 2. It is suggested that IgE denaturation is the consequence of interactions between molecules of immunoglobulin and that such interactions are diminished by steric hindrance in a medium containing high concentrations of ions or hexose molecules.
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PMID:Influence of the medium on the heat and acid denaturation of IgE. 665 41

BALB/c mice were immunized against a monoclonal antiidiotypic antibody (Id 315.1.4) directed against the myeloma DNP-binding protein MOPC315 (IgA-lambda 2). This antibody is specific for an MOPC315 "private" idiotope, and the expression of this idiotope requires the interaction between MOPC315 heavy and lambda chains. Two categories of antibodies, able to combine with Id 315.1.4, were characterized in the sera of anti-Id 315.1.4 mice: (1) antibodies with a kappa light chain and without detectable anti-DNP function, and (2) antibodies with a lambda light chain and able to combine with DNP antigen. This observation suggests that the idiotypic network is not close-ended for a given idiotypic system but must be connected with other systems.
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PMID:The idiotypic network: the murine MOPC315 anti-DNP system. 698 35

After immunization of mice with 2,4-dinitrophenyl-ovalbumin (DNP-OVA), it was shown previously that strains having Igh-Va genes and able to express light chains of the Vk1 group produce high levels of anti-DNP antibody bearing an idiotype (Id-460) associated with the combining site of the BALB/c DNP-binding myeloma protein MOPC 460. Expression of Id-460 in serum is transient; Id-460 levels peak early in the response and are regulated independently of total anti-DNP antibody. In this paper, the transient dominance of Id-460 expression has been confirmed at the cellular level by inhibition of splenic anti-DNP plaque-forming cells (PFC) with rabbit anti-Id-460 antiserum. Id-460+ PFC can account for 52-91% of anti-DNP PFC early after secondary challenge with DNP-OVA. Furthermore, Id-460 is represented at these high levels in IgM, IgG, and IgG1, and IgG2a, the three isotypes tested in the PFC assay, as well as in IgE, as tested by passive cutaneous anaphylaxis. Thus, there is no preferential association of Id-460 with a given isotype. We conclude from these studies that Id-460 is a dominant idiotype in the anti-DNP antibody response of BALB/c mice to DNP-OVA. This dominance is expressed transiently and is independent of isotype. A further conclusion from these studies is that regulation of isotype expression is independent of the regulation of idiotype expression in this system. We would suggest that regulation of Id-460 expression involves Ig-dependent helper T cells specific for Id-460 that induce Id-460+ B cells and also activate suppressor T cells, both events occurring via idiotype-anti-idiotype interactions.
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PMID:Expression of an idiotype (Id-460) during in vivo anti-dinitrophenyl antibody responses. II. Transient idiotypic dominance. 702 12

Passively transferred MOPC 315 IgA myeloma protein accelerated the elimination of DNP-ovalbumin, to which the myeloma protein bound with antibody-like affinity, from the circulation and increased the subsequent antibody response to hapten and to carrier, when injected with or without adjuvant.
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PMID:Immune elimination and enhanced antibody responses: functions of circulating IgA. 742 38

Spleen cells from BALB/c mice immunized with MOPC 315 IgA were fused with P3X63/Ag8 myeloma cells. Hybrid clones were screened for antibody production by a plate-binding radioimmunoassay in which MOPC 315 IgA was reacted with culture supernatants and 125I-protein A. One antibody-producing hybridoma clone (D10) was selected and injected i.p. into BALB/c mice. Ascitic fluid of tum or-bearing animals reacted specifically with MOPC 315 IgA and the reaction was inhibited by DNP- aminocaproic acid, indicating that the monoclonal antibody was directed against the hapten-binding site of MOPC 315 IgA. The monoclonal antiidiotypic antibody was of the complement (C)-binding IgG2a subclass and inhibited IgA production and growth of MOPC 315 cells in vitro in the presence of guinea pig C, as assessed by inhibition of formation of plaques and colonies by MOPC 315 cells in agar.
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PMID:A monoclonal antiidiotypic antibody to MOPC 315 IgA inhibits the growth of MOPC 315 myeloma cells in vitro. 745 62

We had previously shown (i) that conjugates of a given antigen A (AgA) and monomethoxypolyethylene glycol (mPEG) induced AgA-specific tolerance in mice which was mediated by polyclonal CD8+ suppressor T (Ts) cells, as well as by soluble factor(s) of these cells (TsF), and (ii) that clones of nonhybridized CD8+ Ts cells could be derived from the above single cells, and monoclonal AgA-specific TsF could be released from these cloned cells. In the present study, we demonstrate that mice pretolerized by injection of AgA(mPEG)n are also unresponsive to an unrelated antigen B (AgB), or to its haptenated derivative AgB-Hpn, when AgB or AgB-Hpn is injected in the form of a covalent adduct with AgA, i.e., AgA-AgB or AgA-AgB-Hpn, but not when it is injected as a mixture with AgA; in this study human (myeloma) IgG (HIgG) served as AgA, and ovalbumin (OVA) or OVA-DNP3 served as AgB or AgB-Hpn. Moreover, this phenomenon was reproduced in vitro; i.e., Ts cells of mice tolerized with HIgG(mPEG)30, or the soluble monoclonal TsF of cloned Ts cells, exerted their associative suppressive effector function--in the obligatory presence of CD8+ T cells of syngeneic naive mice (Tn cells)--on antibody (Ab) formation to an Hp (DNP), when the Hp was present as a covalent adduct linked either directly to HIgG (e.g., HIgG-DNP7) or indirectly via OVA (as in HIgG-OVA-DNP3); however, no suppression of the anti-DNP Ab response was observed when OVA-DNP3 was present as a mixture with HIgG. Furthermore, it was established that the accessory cells involved in processing the specific Ag in the presence of the Ts cells were also downregulated, as reflected by their reduced capacity for presentation of the Ag to HIgG-specific helper T (Th) cells in proliferation assays. All these results demonstrate that (i) the phenomenon of linked immunological suppression may involve the downregulation of Th cells which recognize, concomitantly with the Ts cell, the appropriate epitopes of AgA and AgB on the same Ac cell, (ii) the downregulation of these Th cells may be a consequence of the downregulation of Ac cells by Ts cells interacting with the appropriate epitope(s) present on the Ac cells, and (iii) most remarkably the CD8+ Ts cells could be substituted by Tn cells "armed" with the specific monoclonal TsF.
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PMID:Antigen-specific suppressor factors of noncytotoxic CD8+ suppressor T cells downregulate antibody responses also to unrelated antigens when the latter are presented as covalently linked adducts with the specific antigen. 834 65

Disulfide bonds are a major force in stabilizing the three-dimensional structure of immunoglobulins. To determine the pattern of interchain disulfide bonding between the four H chains, four L chains and single J chain of rat dimeric IgA (dIgA), we analyzed dIgA from the LO DNP-64 hybridoma by diagonal SDS-PAGE. Bands corresponding to one, two, three and four H chains, one and two L chains and the free J chain were observed under non-reducing conditions, suggesting that the interchain disulfide bonds in rat dIgA are unstable under denaturing conditions. Similar patterns of disulfide bonding were observed in three other hybridoma or myeloma dIgAs from LOU/CN rats. In contrast, when dIgA pretreated with iodoacetamide (IA) was analyzed by the same technique, only bands corresponding to four H chains, one and two L chains and the free J chain were observed, suggesting that blocking free sulfhydryl groups stabilizes the inter-H chain disulfide bonds. Reaction of dimeric LO DNP-64 dIgA with 5,5'-dithiobis-(2-nitrobenzoic acid) or with 14C-IA demonstrated that this dIgA contains an average of 4 moles of free sulfhydryl groups per mole of protein under non-denaturing conditions and 9 moles of free sulfhydryl groups under denaturing conditions. Taken together, the results suggest that interchain disulfide bonds in rat dIgA are unstable, presumably due to the influence of nearby free sulfhydryl groups, and that non-covalent forces are critical for stabilizing the dIgA complex. The results also indicate that J chain is entirely non-covalently associated with the H chains, an apparently unique feature of rat dIgA. A model for interchain disulfide bonding in rat dIgA is proposed.
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PMID:Unstable inter-H chain disulfide bonding and non-covalently associated J chain in rat dimeric IgA. 1269 23


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