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)

Murine B lymphoma cultured cell lines bearing membrane IgM and lacking the ability to secrete measurable amounts of IgM were fused with drug-resistant cell lines derived from the IgG2b-producing MPC-11 myeloma. Many of the hybrid clones synthesized and secreted large amounts of IgM, as judged by radial and double immunodiffusion in agar of culture supernatants and by polyacrylamide gel electrophoresis of biosynthetically labeled IgM. When fused with an IgG2b-producing myeloma, many of the hybrids also produced IgG2b, indicating that there was no suppression of the parental IgG synthesis in the hybrids. The amount of IgM or IgG2b secreted by the hybrids was higher than that secreted by myeloma cell lines. The synthesis of the gamma2b heavy chain of the MPC-11 myeloma was not reexpressed by fusion of a gamma2b nonproducer myeloma cell variant with B lymphoma. No other classes of Ig heavy chains, besides the gamma2b and the mu chains, were found to be secreted by any of more than 100 B lymphoma--myeloma hybrids examined. The results of the present work suggest that myeloma cells may fuse not only with normal plasma cells but also with less-mature normal B lymphocytes and that this fusion "induces" the maturation of B lymphocytes into IgM-secreting cells.
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PMID:Induction of amplified synthesis and secretion of IgM by fusion of murine 'b lymphoma with myeloma cells. 31 76

Two mutant cell lines derived from the MPC-11 mouse myeloma synthesize immunoglobulin with abnormal heavy chains and normal light chains. The defective heavy chains have molecular weights of 38,000-42,000 (M3.11) and 50,000 daltons (ICR 11.19) as compared to 55,000 daltons of the wild-type. The glycosylation of the defective heavy chains demostrated several unusual features: first, 30-50% of the M3.11 heavy chain contained no carbonydrate, while 100% of the wildtype and ICR 11.19 heavy chains were glycosylated; second, the glycopeptides of the M3.11 heavy chains revealed an altered gel filtration pattern when compared with the wild-type; and third, digestion with an endoglycosidase indicated that the heterogeneity of the wild-type and M3.11 glycopeptides involved structural changes in the core region of the oligosaccharide. Examination of two other glycoproteins (the major histocompatibility complex antigens) in these cell lines showed that in M3.11, the H-2D but not the H-2K product was abnormally glycosylated and contained a smaller glycopeptide. However, in a subclone of M3.11 that had lost the ability to produce immunoglobulin heavy chains, the H-2D glycopeptide had returned to wild-type size. We concluded from these studies that the defective M3.11 immunoglobulin heavy chain interfered both with its own glycosylation and the glycosylation of another protein, H-2D.
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PMID:Abnormalities in the glycosylation of immunoglobulin heavy chain and an h-2 transplantation antigen in a mouse myeloma mutant. 40 5

The mRNA coding for the kappa-type constant region (C(kappa)) was purified from two clones derived from the MPC-11 mouse myeloma. This mRNA directs the cell-free synthesis of a C(kappa) precursor (molecular weight, about 15,000) in which an extra piece, 17 residues long, precedes the NH(2)-terminal residue (Ala(109)) of the C(kappa) region. The partial sequence of the extra piece is: Met-X-Thr-Asp-Thr-Leu-Leu-Leu-Trp-Val-Leu-Leu-Leu-Trp-Val-Pro-X- (X is unknown). Met(1) was shown to be the initiator methionine. The sequence of the C(kappa) extra piece is completely different from any known sequence preceding residue Ala(109) in whole light (L) chains, thus establishing that the C(kappa)-region mRNA could not have originated from mRNA coding for the whole L chain. The structural features of the C(kappa) extra piece (marked hydrophobicity, size, and a methionine at the NH(2)-terminus) are identical to those characteristic of the NH(2)-terminal extra piece linked to the variable (V) region of whole L-chain precursors. In addition, the C(kappa) extra piece and the extra piece linked to the V region of MOPC-321 L chain have 70% sequence homology. These findings can be explained by the two genes-one Ig chain hypothesis, if we assume that the DNA coding for the extra piece (xp-DNA) is a constitutive part of the V gene. According to this model, the C(kappa)-region mRNA could have originated from: (i) translocation of this V gene to the C gene, deletion of the entire mature V gene, and "end-to-end" repair of the remaining xp-DNA to the C gene; (ii) translocation to the C gene only of the xp-DNA portion of the V gene. Alternatively, we may assume that the xp-DNA is not covalently linked to the mature V gene at all times, as might be the case for the DNA of hypervariable regions presumed to be in episomes. This raises the intriguing speculation that the xp-DNA represents a third distinct gene, designated xp-gene. The presumed xp-gene may be involved in the regulation of gene transcription: when linked to the mature V gene it initiates a chain of events leading to whole L-chain mRNA formation; when attached to the C gene it leads to its transcription to provide the C-region mRNA.
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PMID:Independent expression of the gene coding for the constant domain of immunoglobulin light chain: evidence from sequence analyses of the precursor of the constant region polypeptide. 41 16

MPC 11 mouse myeloma cells synthesize two immunoglobulin kappa light chains, coded by two separate genes. One of these Kappa-chains has no variable region and is degraded intracellularly. The other is a full-length kappa-chain contaning both variable and constant regions: this chain is secreted, both by itself and combined with heavy chains in molecules of immunoglobulin G. This paper reports the amino acid sequence of the myeloma MPC 11 full-length kappa-chain. The chain is unusual in having 12 extra residues at its N-terminus when its sequence is aligned with those of other mouse kappa-chains; no other anomalies were found in its sequence.
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PMID:Sequence of the full-length immunoglobulin kappa-chain of mouse myeloma MPC 11. 41 75

Three mouse immunoglobulins with altered heavy chains have been used to study the specificity of the mouse IgG2b Fc receptor on mouse macrophages. These immunoglobulins were synthesized by variant clones derived from the MPC 11, IgG2b-producing mouse myeloma cell line. One variant, whose Fc receptor. A second variant, which makes a short heavy chain lacking the CH3 domain, binds specifically to the IgG2b Fc receptor. The third variant makes a hybrid IgG2b-IgG2a heavy chain whose CH3 domain is enterely IgG2a-like and binds to both IgG2a and IgG2b Fc receptors. These data suggest that the binding of mouse IgG2b immunoglobulins to the mouse macrophage Fc receptor involves a site within the CH2 domain and indicate that immunoglobulins with altered heavy chains are a useful tool to probe Fc receptors.
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PMID:Site of binding of mouse IgG2b to the Fc receptor on mouse macrophages. 47 65

Protein synthesis in differentiated MOPC-21 and MPC-11 mouse myeloma cells was studied to determine the basis for the differences in the temperature and actinomycin D sensitivity of translation between non-differentiated mouse L-cells and differentiated rabbit reticulocytes. The temperature dependence of total protein synthesis was similar to that of L-cells and reticulocytes, being biphasic in Arrhenius plots with apparent activation energies of approximately 25 and 42 kcal/mol, above and below 25 degress C. The dependence of the secretion process was different since it was not biphasic, having a single activation energy of about 22 kcal/mol. Myeloma polysomes were like L-cell polysomes in their response to lower temperature and reached a minimum level of 50% at 15 degress C. This response was also found for the specific polysomes synthesizing the IgG H- and L-chains. In the presence of actinomycin D, myeloma polysomes declined exponentially with a half-life of approximately 6 hours. These two L-cell-like responses were not found in reticulocytes. Translation of both the IgG mRNAs and the non-IgG mRNAs was reduced by lower temperatures and actinomycin D, even though the L-chain mRNA was slightly more resistant, suggesting that this mRNA is slightly more efficient. The results of these experiments suggest that the translational differences between L-cells and reticulocytes are not mRNA dependent, but are cell type differences.
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PMID:Effect of temperature on protein and immunoglobulin synthesis and secretion in two mouse myeloma cell lines. 51 46

Multiple myeloma is often associated with humoral immunodepression in both man and mouse. When mice bearing the humorally immunodepressive plasmacytomas TEPC-183 and SPQC-11 were injected with SRBC, the rise of serum haemolysins was significantly less than that of non-tumour-bearing mice. Mice with the plasmacytomas MPC-11 and MOPC-315 have an antibody response similar to normal mice when injected with SRBC. Following immunization, normal mice and those bearing MPC-11 showed a 2- to 3-fold increase in total spleen lymphocytes. Mice bearing TEPC-183 or SPQC-11, the plasmacytomas causing an impaired antibody response, has significant increase in spleen lymphocytes under the same conditions. Mice bearing MOPC-315 had a very high initial count of spleen lymphocytes, which did not further increase upon immune stimulation.Incubation of lymphocytes from plasmacytoma-bearing mice with PHA did not produce an increase in TdR incorporation and in some cases even caused a decrease in TdR incorporation.Lymphocytes from mice bearing TEPC-183, SPQC-11, and MOPC-315 incorporated less TdR in response to LPS than did normal mice. On the other hand, mice bearing MPC-11 incorporated about as much TdR as did normal mice following LPS stimulation. Thus, the defect in the ability to respond to LPS in vitro correlated with the lack of an increase of spleen lymphocytes in mice bearing these tumours following antigenic stimulation in vivo.No immunodepressive properties of serum from mice with plasmacytoma could be detected.
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PMID:Lymphocyte defect in plasmacytoma-bearing mice. 64 25

The IgG2b-producing MPC 11 mouse myeloma cell line has yielded a number of variants which synthesize heavy chains characteristic of a different immunoglobulin subclass, IgG2a, as previously shown by serology, peptide maps, and assembly profiles. We have studied the Fc regions of the IgG2a protein synthesized by one variant, ICR 9.9.2.1, and of the IgG2b protein synthesized by MPC 11 and compared them to MOPC 173, an IgG2a protein of known sequence. We analyzed the Fc regions of the three immunoglobulins by several analytical techniques, such as immunoelectrophoresis of papain digests, NaDodSo4-polyacrylamide gel electrophoresis analyses of Fc CNBr fragments, and comparative ion-exchange chromatography of radiolabeled tryptic and chymotryptic Fc peptides. In addition, Fc CNBr fragments of the variant gamma2a and MPC 11 gamma2b molecules were isolated and subjected to amino acid analysis and partial sequence determination. From these data, we concluded that the Fc fragment of ICR 9.9.2.1 is most probably identical to that of MOPC 173 and different from the parental gamma2b Fc fragment. A number of residue positions which discriminate between gamma2b and gamma2a sequences are described. In two of three segments sequenced, gamma2b and gamma2a molecules share more identical residues than either shares with another mouse subclass, gamma1.
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PMID:An IgG2a-producing variant of an IgG2b-producing mouse myeloma cell line. Structural studies on the Fc region of parent and variant heavy chains. 70 16

Mouse myeloma tumors and some variants derived from them were labeled in vitro with tritiated leucine and the radioactive J chain was assayed in cell lysates by precipitation with an antiserum specific for mouse J chain. The major findings were: 1) J chain can be found in an IgG2b-secreting cells (MPC-11). These data, together with previous findings suggest that cells secreting all classes of IgG synthesize J chain, even though there is no apparent requirement for J chain in assembly of the IgG molecule. Hence production of J chain does not depend upon secretion of a polymeric immunoglobulin. 2) Intracellular J chain can be found in myeloma variants that do not produce heavy chains showing that production of J chain may not coordinately be linked to the synthesis of heavy chain. 3) J chain was found in cells synthesizing, but not secreting, immunoglobulin. Thus production of J chain is not linked to secretion of immunoglobulin. 4) J chain could not be detected in plasma cells that do not produce immunoglobulins. It was also not found in mouse leukemic cells, suggesting that production of J chain is probably linked in some way to immunoglobulin production.
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PMID:Control of J chain biosynthesis in relation to heavy and light chain synthesis, polymerization and secretion. 80 6

Cells of the MPC-11 mouse myeloma cell line, which produces an IgG2b immunoglobulin, were subjected to mutagenesis with Melphalan or with ICR-191, after which they were cloned in soft agar. Approximately 0.5 percent of the clones produced altered heavy chains that: (i) were the same size as or larger than the parent; (ii) no longer recognized by antibody specific for the parent gamma2b subclass; (iv) were recognized by antibody against the Fab (NH2-terminal half) of the parental immunoglobulin, but lacked some of the antigenic determinants of the Fc (COOH-terminal half) of the heavy chain; (v) lacked many of the tryptic/chymotryptic peptides found in the parent; (vi) contained tryptic/chymotryptic peptides that were not present in the parent but were present in an unrelated gamma2a myeloma heavy chain; and (vii) assembled with light chains by a pathway typical of IgG2a myelomas.
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PMID:Variants of a mouse myeloma cell line that synthesize immunoglobulin heavy chains having an altered serotype. 80 28


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