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)

Spontaneous variants of the IgA immunoglobulin secreting mouse myeloma, S194-2, were isolated by cloning the line on soft agar and screening for the loss of secreted S194 immunoglobulin. Because S194 IgA possesses DNP binding activity, the screening method was designed to test for clonal secretion of antibody which specifically precipitated DNP-ferritin conjugates. Precipitates formed over IgA secreting S194 clones, whereas none were evident over nonsecreting XCl clones nor IgG secreting MOPC 21 clones (MOPC 21 IgG does not bind DNP). In addition the method was sensitive to the amount of immunoglobulin secreted. By continual selection of exceptionally reactive clones with this assay, a S194 culture was obtained which secreted five to six times as much IgA as the original mass culture. Spontaneous variants were isolated from six independent subclones of this parent line with an overall frequency estimated at 2.7 X 10(-5) per cell per generation. Biochemical analysis of these variants showed that all of them secreted reduced or undetectable amounts of IgA. No variants were obtained which secreted IgA molecules altered at the DNP binding site, or which secreted immunoglobulin subunits alone. Variants of the latter class have, however, been obtained in high frequency in other myeloma strains by other investigators.
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PMID:A screening method to detect clonal secretion of DNP-specific antibody. 110 44

The effect of specific immunoglobulin (Ig) on specific binding of antigen to cells has been studied in a model system consisting of nurine myeloma cells (MOPC 315), MOPC 315 serum, and DNP conjugates. MOPC 315 serum, which has IgA specific for DNP, specifically inhibited the binding of DNP conjugates to these cells. Using this model it was found that cells have a marked advantage over free specific Ig in binding multivalent antigen molecules and retaining them in a bound state. Cells were able to specifically bind multivalent antigen in the presence of a large excess of free specific Igm the kinetics of antigen binding to cells was slow, and prolongation of time of incubation increased the amount of specific binding. Both antihapten and anticarrier Ig augmented nonspecific binding of multivalent but not of univalent hapten to control cells. Furthermore, antihapten Ig at low concentration increased antigen binding to specific cells.
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PMID:Binding of antigen by immunocytes. II. Effect of specific Ig on antigen binding by MOPC 315 cells. 116 94

BALB/c mice with the plasmacytoma MOPC 104E producing monoclonal IgM-lambda with antibody activity to alpha-1,3 dextran were found to have B lymphocytes with surface immunoglobulins with the immunochemical characteristics of 104E IgM capable of binding alpha-1,3 dextran. RNA extracted from this plasmacytoma induced the synthesis of such surface immunoglobulins on normal B lymphocytes in vitro and in vivo. Injection of 200 mug of MOPC 104E RNA into normal mice 72 hr prior to the administration of the antigen kept the immune response to dextran-S intact, but suppressed that to other antigens, such as DNP-Ficoll and LPS, T cell-independent antigens, and SRBC and BSA which are T cell-dependent. The effect of the RNA was abolished by RNase but not by pronase and DNase. RNA extracted from LPC-1 tumour (gamma2a-k without known antibody activity) significantly suppressed the immune response to dextran-S and to other antigens in normal mice. Thus, opposite effects of MOPC 104E RNA on the response to specific and non-specific antigens strengthen the hypothesis that the immune deficiency in plasmacytoma bearing mice is due to the conversion of normal surface immunoglobulin of a population of B lymphocytes to the idiotype of the respective myeloma globulin.
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PMID:Surface immunoglobulins of lymphocytes in plasmacytoma. V. The effect of RNA-rich extract from mouse plasmacytoma MOPC 104E on the immune response. 127 83

368 1- to 5-year-old mink of wild-type or black genetic background were infected with Aleutian disease virus (ADV) naturally or using virus-containing immune complexes or purified virus. Thirty of the mink were immunized with dinitrophenol-conjugated ovalbumin (DNP-OA) before and during infection. Blood samples were taken at monthly intervals. We found that weak (and transient) monoclonal or oligoclonal immunoglobulin components were present in the plasma or serum approximately 1 month after infection, as judged by zone electrophoresis. In a few cases, we found quite stable myeloma-like hypergammaglobulinemia, which usually occurs much later in the infection. All sera with monoclonal immunoglobulin components and most of the sera with immunoglobulins of restricted heterogeneity were analysed by crossed serum line immunoelectrophoresis. In all cases, the distinct immunoglobulins were found to have antibody activity to ADV proteins. In the few sera from DNP-OA-immunized mink showing restricted immunoglobulin heterogeneity, this was also the case. The findings from the study imply that ADV-specific B lymphocytes are probably the primary targets for ADV. The resulting ADV replication introduces a "pseudo-transformation" stage, so that the infected B lymphocytes proliferate and differentiate to an extreme degree. The mechanism behind this B-cell pseudotransformation ability of ADV is a puzzle. It may, however, be important, that the p75/85 structural polypeptides of ADV contain an amino acid sequence almost identical to the GTP-binding pocket of the Ras oncogene.
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PMID:Virus-specific B-lymphocytes are probably the primary targets for Aleutian disease virus. 165 Oct 29

Contact hypersensitivity (CS) to 2,4-dinitrofluorobenzene (DNFB) in BALB/c mice is regulated by autoanti-idiotypic antibody. This report describes the preparation and characterization of a monoclonal antibody, 2-16.1, which has characteristics previously described for the serum anti-idiotypic antibodies. Monoclonal 2-16.1 was prepared by fusing lymph node (LN) cells from optimally sensitized BALB/c mice to the P3X myeloma. The monoclonal product of the cloned hybridoma is an IgM (K) immunoglobulin which does not bind to DNP-protein but which does bind to other immunoglobulins with anti-DNP specificity, primarily of the IgM class. Functionally, 2-16.1 inhibits the efferent limb of the CS reaction as measured by passive transfer of immunity. This inhibition is antigen-specific and appears to require the presence of a subset of Ia+ T cells in the DNFB-immune LN cell population. Suppression of transfer of immunity is strain-specific. Finally, suppression occurs only in the absence of complement, indicating that a lytic mechanism is not involved and that 2-16.1 does not recognize determinants expressed on the effector T cells of the CS reaction. Collectively, these results indicate that 2-16.1 is a monoclonal anti-idiotypic antibody, and that the hybridoma CSDNP 2-16.1 represents a clone of B cells which is stimulated during the primary CS response to DNFB and whose antibody product is involved in the endogenous, active regulation of this T cell-mediated response.
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PMID:Antibody-mediated regulation of T cell responses. I. Characterization of a monoclonal antibody which specifically regulates contact hypersensitivity to DNFB in BALB/c mice. 242 89

Electrofusion of mammalian cells in strongly hypo-osmolar media containing sorbitol, small amounts of divalent cations and albumin resulted in high yields of hybrids. The number of viable hybrids was higher than any value for chemically- or electrically-mediated fusion reported in the literature. Optimum clone numbers were obtained for fusion of osmotically-stable subclones of murine myeloma cells with DNP-Hy-stimulated lymphocytes provided that the osmolarity of the fusion medium was as low as 75 mosmol/l. Similar results were obtained for fusion of osmotically stable subclones of myeloma cells with the murine hybridoma cell line G8. Due to the dramatic increase in volume the field strength of the breakdown pulse (leading to fusion of the dielectrophoretically aligned cells) has to be reduced, as predicted by theory. The efficacy of hypo-osmolar electrofusion allowed the use of very few cells (about 10(5) lymphocytes or G8 cells per fusion chamber). This figure is considerably smaller than that reported in the literature for iso-osmolar electrofusion. It is significant that, in contrast to iso-osmolar conditions, the fusion yield in hypo-osmolar electrofusion was reproducible over long periods of time and less dependent of variations between cultures. At suspension densities of about 10(6) cells per fusion chamber (normally used in iso-osmolar electrofusion) hypo-osmolar electrofusion of homogeneous cell suspensions resulted in the formation of many giant cells when the appropriate field conditions were applied. Similar high or, at some field strengths, even higher numbers of clones at low cell suspension density were obtained when G8 and myeloma cells were first exposed during the washing procedure to strongly hypo-osmolar media, but then transferred to iso-osmolar solutions for electrofusion. Similar experiments with lymphocytes and myeloma cells failed because of destruction of many lymphocytes by the two osmotic shock steps in rapid succession. Volume distribution measurements of G8 and myeloma cells showed that after re-incubation of the osmotically pre-stressed cells the original volume distribution is largely, but not completely re-established. This and other results indicate that osmotic pressure gradients and associated tensions in the membrane do not play a primary role in the initiation of the electrofusion process. The experiments suggest that due to the osmotic (pre-) stress the membrane permeability is slightly and uniformly increased presumably due to the dissolution of membrane- and cell-skeleton proteins. Obviously, this facilitates electrofusion in hypo-osmolar or subsequently in iso-osmolar solutions.
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PMID:Enhanced hybridoma production by electrofusion in strongly hypo-osmolar solutions. 275 49

The urinary light chain dimer and serum monoclonal IgG1 protein from a patient (Mcg) with multiple myeloma and amyloidosis were systematically tested for their binding activities to peptides presented on solid supports. The system was validated using a series of enkephalins, beta-casomorphins and DNP-lysine derivatives which were known to complex with the dimer. Sets of peptide ligands binding to the proteins were constructed by incremental additions of amino acid residues to minimal binding units [Geysen et al., J. Immun. Meth. 102, 259-274 (1987)]. Both the amino acid sequences and the combinations of optical isomers were optimized at each stage of the syntheses. Binding could be demonstrated for ligands ranging in size from a tethered single amino acid to pentapeptides. At the dipeptide levels, the dimer and the IgG1 protein showed different preferences (Hp versus qf, where lower case letters designate D-amino acid residues). However, in a tetrapeptide ligand (qfHp) for the dimer, both of these initial preferences had converged. With few exceptions, the IgG1 molecule showed binding activity for the ligands developed for the dimer. Two sets of selected peptides, one based on Hp and the other on mW, were synthesized for diffusion into crystals of the dimer. X-ray analyses showed that these peptides bound exclusively in the main binding cavity between the "variable" domains of the dimer. As predicted from the ELISA results with tethered ligands, the relative occupancies in the crystals followed the order of tetrapeptide greater than tripeptide much greater than dipeptide. The crystallographic studies confirmed that peptides with very different sequences can bind in the same cavity.
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PMID:Similar binding properties of peptide ligands for a human immunoglobulin and its light chain dimer. 277 86

V kappa Ig germ-line genes have been isolated from recombinant clones prepared in separate libraries constructed from adult BALB/c liver DNA. Three different clones that strongly hybridized with a V kappa-GAT-specific probe were completely characterized and sequenced. All three genes exhibited common characteristic features in their sequences encompassing the 5' to the 3' noncoding region, with coding sections 95% homologous. A comparison with other V kappa genes shows that the size of the first intron is variability subgroup specific. Moreover, a direct correlation exists between the size of this intron and the entire length of the coding region. Nucleotide sequences of these genes were compared with V kappa chains expressed at the Ab1 and Ab1' levels of the GAT idiotypic network: Ag----Ab1----Ab2----Ab3 (Ab1'). K1A5 and K5.1 genes account for V kappa chains in Ab1 and Ab1' hybridomas, respectively. The high conservation of Ab1' sequences in light chain was also recently reported for the heavy chains, suggesting that immunization with Ab2 (anti-idiotypic) antibodies preferentially stimulates the direct expression of germ-line genes. K5.1 and K1A5 genes belong to the V kappa-1 variability subgroup and encode, without any amino acid substitution, V kappa domain in myeloma TEPC 105 and MOPC 467, which are V kappa-1A and V kappa-1C subgroup prototypes, respectively. These genes are extensively used in different mouse strains and in a number of antibodies of discrete specificities, such as anti-GAT, anti-DNP, anti-flagellin, anti-phosphorylcholine, anti-digoxin, anti-phenyloxazolone, and anti-DNA.
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PMID:Two V kappa germ-line genes related to the GAT idiotypic network (Ab1 and Ab3/Ab1') account for the major subfamilies of the mouse V kappa-1 variability subgroup. 310 Jun 21

Amino terminal amino acid sequences were obtained for both the heavy (H) and light (L) chains of seven BALB/c anti-arsonate (Ar) monoclonal antibodies representing the 5AF6 and 3C6 idiotype (id) families described in this strain. 5AF6 family H chains showed strong homology to the germ-line gene sequence for the A strain 36-60 family. However, four to five identical H chain sequence differences for two of these antibodies (5AF6 and 95B5), as well as two previously reported related sequences (92D5, 94B10), suggested they were encoded by a different Vh. The 36-60 family Vh genes have been shown to be identical to the Vh gene of the anti-DNP binding myeloma M460 [Dzierzak et al., J. Immun. 136, 1864-1870 (1986)]. H chains amino acid sequences derived from an id-460+ anti-DNP hybridoma and a germ-line gene differing from the 30-60-like Vh sequence [Dzierzak et al., J. Immun. 136, 1864-1870 (1986)] were found to be virtually identical to the 95B5 and 5AF6 Vh sequences. This suggests that the same two related H chains making up two subsets of the 5AF6 anti-Ar id family are also both used in two subsets of the id-460 anti-DNP response. 5AF6 family L chains were highly homologous to the other Vk2 L chains of the 36-60 family. 3C6 family H chains can be placed in the Vh l group, are unrelated to the described anti-Ar H chain families, and have been placed in a new anti-Ar Vh family, Ars-E. The 3C6 H is similar, however, to a Vh used by a BALB/c anti-GAT idiotype family of antibodies. 3C6 L chains were of the murine kappa chain group, Vk8 and most resembled an L chain from an A strain monoclonal anti-Ar having no defined idiotype.
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PMID:Two BALB/c anti-arsonate idiotype families: two heavy chain variable regions (Vh) shared with anti-DNP antibodies are used by one family while a Vh similar to anti-GAT antibodies is used by the other. 311 3

We have previously reported that T helper cells of BALB/c mice recognize the unique mutated sequence Phe94, Arg95, Asn96 of the lambda 2 L chain of isologous (BALB/c) myeloma protein 315. Here we study two Id (Id-315.1.4 and Id-315.TH) of the DNP-Lys binding M315 defined by two monoclonal isologous anti-Id Ab (Ab 2-1.4 and Ab 2-TH). Both Id were (1) totally expressed by Fv-315, but not by free unpaired V domains, (2) specifically dependent on VH-315, since lambda 2-315 recombined with four other H chains did not express the Id, (3) related to the hapten-binding site because their expression was blocked by the haptens DNP-Lys and DNP-Gly, and (4) topographically related because Ab 2-1.4 and Ab 2-TH competed with each other for binding to M315. The contribution of lambda chain V regions was studied with the aid of reconstituted Ig molecules of H-315 paired with lambda 1, lambda 2, and lambda 3 L chains. Id-315.TH was expressed equally well by reconstituted Ig containing three different lambda 2 chains (lambda 2-5-7, lambda 2-T952, and lambda 2-315), but its expression was profoundly reduced when H-315 was associated with lambda 3-SAPC15 or lambda 1-J558 L chains; it therefore depended upon amino acids encoded by germline lambda 2 genes. By contrast, Id-315.1.4 was only restored by the lambda 2-315 chain paired with H-315. Since lambda 2-5-7 and lambda 2-T952 differ from lambda 2-315 at positions 38, 94, 95, 96, and 98 or 99, respectively, Id-315.1.4 probably requires the unique mutated amino acids Phe94, Arg95, Asn96 of lambda 2-315. This resembles the effects on Id expression of previously reported unique amino acids of the D region. We failed to confirm that hyperimmunization of BALB/c mice with Ab 2-1.4 cross-linked to KLH induced M315-like Ab. The results are discussed in terms of the contribution of the third hypervariable loop of lambda chains to Id and the immunogenicity of isologous Ig.
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PMID:Two M315 idiotopes defined by isologous monoclonal antibodies: one depends on germline and the other on mutated murine lambda 2 light chain sequences. 312 Mar 5


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