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 localization of a major determinant on an isologous myeloma protein (M315) which stimulates BALB/c helper T cells was investigated. Augmentation of the adoptive secondary antibody response to NIP-M315 and the idiotype of M315 (Id315) was used as an indicator of helper effects. Spleen cells primed with the light chain of M315 (L315) and its V-domain (VL315) were highly efficient helpers; priming with the fragment containing the two V-domains of M315 (FV315) induced a somewhat weaker helper effect than L315 or VL315. The helper effect was abolished or markedly reduced by treating the primed cells with rabbit anti-brain theta + C. Cells primed with the heavy chain of M315 (H315) effected weak but significant help. The V-domain of H315 (VH315) was incapable of eliciting cells with detectable helper effect. The data indicate that the VL315 embodies a major determinant for T helper lymphocytes. This determinant is expressed on the free VL315 as well as on the complete M315. In contrast, previous studies have shown that BALB/c antibodies produced against Id315 recognize antigenic sites that are only displayed on associated (VL315 + VH315) domains.
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PMID:T helper lymphocytes recognize the VL domain of the isologous mouse myeloma protein 315. 9 75

Six hundred and twelve mouse plasmacytomas were screened for hapten binding by using eleven different bacteriophage-hapten conjugates (phage T4 conjugated with haptens NP, NIP, DIP, DNP,BOC-ABA-Tyr, ABA-NP, ABA-MIP, ABS-HOP, PAB-HOP, penicillin G, cloxacillin). Fifteen ascites fluids (2.4%) inactivated at least one of the phage conjugates at a high dilution indicating binding. The specificity of these reactions was studied by titrating one ascites fluid with phage conjugates carring unrelated haptens, and by inhibiting the phage inactivation with free haptens. Of the 15 myeloma proteins, 10 had high titers (at least 30 times higher than the ascites fluid background) with the NIP-cap phage or the NP-cap phage or both. Four had high titers with the DNP-cap phage and one with the ABA-MIP phage. Thirteen of the 15 myeloma proteins were IgA, one was IgM and one IgG2b.
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PMID:A search for hapten-binding mouse plasmacytoma proteins. 43 27

Spleen cells from adult unprimed outbred (Swiss) and inbred (BALB/c) mice, either normal (no) or athymic-nude (nu) as well as spleen cells from Swiss nude mice bearing two different human tumors (BUR and PINQ), were fused with the mouse non-secreting myeloma cell line P3X63 Ag8-653. The supernatants of immunoglobulin secreting hybrids, all containing IgM, were screened for antibody activity against macromolecular antigens (autologous: actin, tubulin, myosin, dsDNA) and haptens (TNP, NP, NIP and NBrP). Furthermore, their idiotypic determinants were analyzed using a rabbit anti-idiotype which recognizes a major cross-reactive idiotype (IdD23) of BALB/c natural polyreactive autoantibodies. In all the mice studied, we identified: (1) hybrids reacting strongly with one or more haptens (10.7 to 37.8%) and (2) hybrids secreting natural monoclonal autoantibodies (NMoAb) with broad reactivities (polyreactive and/or oligoreactive) against autoantigens and/or haptens (11.4 to 26.8%). The results indicate that: (1) cells secreting natural autoantibodies with broad reactivities exist in both normal and nude mice, independently of the genetic background (inbred/outbred) of the mouse. However, in nude mice, the natural autoantibodies exhibit a more restricted pattern of reactivity (oligoreactive) compared to those of normal mice, and do not express the common idiotype IdD23 of natural polyreactive autoantibodies. (2) Tumors grafted into nude mice seem to induce the expression of polyreactive autoantibodies bearing the IdD23.
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PMID:Natural autoantibodies in nude and normal outbred (Swiss) and inbred (BALB/c) mice. 276 99

We have constructed a chimeric aequorin consisting of a fragment of the anti-NP immunoglobulin gene fused to the aequorin gene. Expression in a myeloma cell line has produced a Fab'-like molecule that has the ability to bind NIP specifically and generate bioluminescent activity. It takes approximately 8 h at 4 degrees C in the presence of 2-mercaptoethanol and coelenterazine to regenerate luminescent activity. While the flash kinetics of this recombinant molecule are similar to native aequorin, its quantum efficiency is ten times lower. Preliminary studies have been conducted to ascertain its usefulness for immunoassays. We have shown for this chimeric aequorin 7 x 10(-19) moles can be detected in solution, also it can be used in a solid-phase assay and is stably stored at -70 degrees C for at least 2 months.
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PMID:Characterization of a chimeric aequorin molecule expressed in myeloma cells. 280 Dec 22

H-2-linked immune response (Ir) genes control T helper cells (Th) that recognize idiotopes of the V domains of myeloma protein 315 as carriers; Th recognition was detected by augmentation of antibody responses of hapten (4-hydroxy-3-iodo-5-nitrophenylacetyl (NIP]-primed B cells boosted with NIP conjugated to Fab315. The present study indicates that the responder k allele of the Ir VH315 gene maps to the I-A subregion of H-2. A responder s allele of the Ir V lambda 2(315) gene on an A-strain background was identified, which also most likely maps to I-A. Although the d allele of the Ir V lambda 2(315) gene is a responder allele on DBA/2 background, the D2.GD strain (with I-region haplotype AdBbJbEbCb) was non-responder to V lambda 2(315), suggesting either that the responder d allele maps to I-E or that the b allele of a second Ir V lambda 2(315) gene located to the right of I-A exerts a strong suppressive influence. The H-2b haplotype conferred non-responsiveness to VH315, V lambda 2(315), and Fv315.
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PMID:H-2-linked Ir genes have a striking influence on the immunogenicity of idiotopes of myeloma protein 315 for T helper cells. 315 1

Spleen cells derived from BN rats receiving HgCl2 were fused with the nonsecreting rat myeloma cell line IR983F. We screened 59 supernatants from immunoglobulin-secreting hybrids for antibody activity against actin, tubulin, autologous and heterologous myosin, myoglobin, dsDNA, peroxidase, and the haptens TNP, NIP, NNP, and NBrP. Six monoclonal antibodies (mAb) were found to react with antigen(s) of the panel. At least three groups of antibody specificities were identified: clones reacting with TNP (1 IgM, 1 IgE); clones reacting with horseradish peroxidase (1 IgM); and clones possessing widespread reactivity for several antigens as found for mouse natural autoantibodies (2 IgM, 1 IgE). We also analyzed the idiotypic (Id) determinants of the 59 mAb by using anti-Id antibodies described elsewhere prepared in rabbits against the BALB/c D23 natural monoclonal autoantibody and recognizing a BALB/c recurrent Id (Id D23) of natural polyspecific autoantibodies. We found that all rat mAb that possessed widespread reactivities bore this Id. We performed similar studies in sera from normal and mercury-stimulated rats. The results indicate a role for HgCl2 in the stimulation of natural antibodies producing cells and the existence of interspecies cross-reactive Id among mouse and rat natural antibodies.
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PMID:Autoimmunity induced by HgCl2 in Brown-Norway rats. II. Monoclonal antibodies sharing specificities and idiotypes with mouse natural monoclonal antibodies. 351 56

Previous studies from this laboratory have revealed an antigenic site located on the variable domain of the lambda 2 light chain of BALB/c myeloma protein 315 (the V lambda 2(315) site). This site is recognized by conventional carrier-specific T helper cells (Th) of BALB/c mice and is expressed on both the free and assembled V lambda 2(315) domain. The present work defines two new antigenic sites associated with murine lambda chains. The first site was associated with free lambda 1-chain of myeloma protein J558. It was recognized by splenic Th from animals that had been primed with free lambda 1J558 in complete Freund's adjuvant; when transferred to irradiated animals the primed Th responded to a boost with (4-hydroxy-5-iodo-3-nitro-phenyl)acetate (NIP)-free lambda 1J558 in saline, but did not respond to NIP-complete J558 or NIP-free lambda 2(315). Priming with complete J558 failed to elicit Th that responded to NIP-free lambda 1J558. This determinant was therefore only expressed on the free (as opposed to the assembled) form of lambda 1J558, and it was not shared with free lambda 2(315). The second antigenic site was shared between free lambda 1J558 and free lambda 2(315). It was defined by free lambda 2(315)-primed Th which responded to a boost with NIP-free lambda 1J558. Since priming with free lambda 1J558 did not elicit Th that recognized NIP-free lambda 2(315), the cross-reaction was undirectional. The free lambda 2(315)-primed Th failed to respond to the complete J558, and M315-primed Th failed to respond to NIP-free lambda 1J558, indicating that the second (cross-reactive) antigenic site, like the first, was only expressed on free lambda chains. Completely reduced and alkylated (unfolded) free lambda 1J558 and free lambda 2(315) chains elicited Th that recognized native (folded) free chains. Thus, free lambda 1J558 bears two antigenic determinants recognized by Th, one private and a second shared with free lambda 2(315). Lambda 2(315) also bears two determinants, a cross-reactive one on free lambda 2(315) shared with free lambda 1J558, and a private one located on the V lambda 2(315) domain of the complete M315. The discussion is focused on possible explanations for the quenching of the two new lambda chain determinants upon light-heavy chain assembly and why, by contrast, the private V lambda 2(315) site is maintained in the complete M315.
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PMID:Recognition of lambda 1 and lambda 2 murine light chains by carrier-specific isologous T helper cells; effect of L-H chain assembly. 618 25

The specificity of BALB/c antibodies and Th elicited by BALB/c myeloma protein W3129 (alpha, kappa) and its subunits was studied. Antibodies were detected with RIA and ELISA techniques. Th were demonstrated by their ability to augment a secondary anti-NIP antibody response in a Mitchison type assay of adoptive immunity. The major proportion of antibodies elicited by the complete W3129 was directed to an idiotypic determinant(s) that depended on assembled H + L chains. The determinant(s) was probably located in or near the antibody combining site because binding was hapten-inhibitable. A second minor antibody population bound an idiotypic determinant(s) on VW3129H expressed on isolated H-chain as well as on the complete myeloma protein. A third and very weakly reactive set of antibodies was specific for a C alpha antigenic site(s) which was expressed much more efficiently on free than on assembled alpha-chains. The antibody response to free kappa W3129 was directed to idiotypic determinants that were inaccessible in the complete molecule. By contrast, free kappa W3129 elicited Th that responded to an idiotypic determinant(s) on VW3129K; the determinant(s) was expressed on both the isolated chain and the complete W3129, suggesting that Th responded to an idiotope not recognized by B-cells. Priming with free alpha W3129 failed in four out of five experiments to induce Th that responded to the complete W3129, demonstrating that a major difference existed between VH and VL of W3129 regarding their immunogenicity for Th. Nevertheless, free alpha W3129 did elicit antibody responses that displayed high reactivity with the complete molecule, indicating that certain serologically defined antigenic sites on the surface of W3129 are also expressed on isolated alpha W3129. Thus, certain differences were detected as to the specificities of Th and B-cells for W3129 and its subunits since they recognized separate idiotopes located in the VL- or VH-region, respectively. The pattern of Th recognition of W3129 resembled that of another isologous myeloma protein, M315, but was unlike that of a third, J558, previously described from this laboratory.
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PMID:Specificity of antibody and helper T-cell responses to the isologous myeloma protein W3129 and its subunits. 620 54

We have examined the recognition of the variable (V) domain of the heavy (VH) and light (V lambda 2) chains of mouse myeloma protein 315 by helper T cells. Mice were primed with the isolated V domain in complete Freund's adjuvant, and carrier (V domain)-primed spleen cells were transferred together with hapten (NIP)-primed spleen cells to recipient mice that were boosted with NIP3-Fab-315. The helper cell response to both domains was governed by H-2-linked immune response (Ir) genes, and VH-315 and V lambda 2 displayed different Ir phenotypes. H-2k conferred high responsiveness to VH on three different genetic backgrounds, BALB/c, C3H, and B10; mice of the d and b haplotypes were low responders. Conversely, H-2d conferred high responsiveness to V lambda 2 on two backgrounds, BALB/c and C3H, whereas mice of the k haplotype were low responders to this domain. Non-H-2 genes of the B10 background extinguished the helper cell response to V lambda 2 in animals with the high responder d haplotype. The VH Ir gene mapped to the K-A interval of the H-2 complex. Unfolded (completely reduced and alkylated) V domains primed helper cells as efficiently as folded domains for responses to NIP3-Fab-315, indicating that the helper cells recognized an antigenic determinant that was not conformation-dependent. The data indicate that there exists helper T cells which recognize each member of the M315 pair of V domains independent of the other, and that these V domains are recognized like conventional extrinsic protein antigens.
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PMID:Helper T cell recognition of the variable domains of a mouse myeloma protein (315). Effect of the major histocompatibility complex and domain conformation. 697 21

Since the beginning of this century, allergen immunotherapy has been widely used to treat allergic disorders. In addition to the long-term clinical efficacy of this therapy, there are immediate beneficial effects as observed in rush immunotherapy for which there is no clear mechanism. We investigated the direct impact of an Ag on its specific IgE in terms of IgE measurability in immunoassays and subsequent binding of IgE to the high-affinity receptor for IgE. As a model we used a chimeric IgE specific for NIP that exhibits similar biologic properties as serum or myeloma IgE. To mimic particulate and soluble allergens we coupled 15 NIP molecules to BSA. Using this "artificial allergen" we could show that the presence of the Ag reduced the IgE measurability in immune assays. Furthermore, IgE binding to the Fc epsilon RI was 60% inhibited in the presence of the Ag shown with an optical biosensor that monitors molecular interactions. In normal basophils passively sensitized with IgE that was preincubated with the Ag, no sulfidoleukotriene release could be induced. Rush immunotherapy may invoke a similar phenomenon, resulting in the short-term alteration of symptoms by blocking or substantially reducing binding of IgE to its high-affinity receptor. Thus, our result may explain some of the short-term beneficial effects observed in rush immunotherapy.
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PMID:Antigen-specific inhibition of IgE binding to the high-affinity receptor. 767 12


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