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PubMed1982

Suppressor activity of splenic macrophages in murine plasmacytoma (PC) is inhibited by PC specific ligands.

Spleens of BALB/c mice with plasmacytoma contain macrophages (M phi) which were found to suppress the in vitro immune function of normal splenic cells through a diffusible factor. The suppressor activity of these macrophages was reversibly inhibited by ligands specific for the corresponding PC globulin, but not by anti-idiotypic antibody. Anti-idiotypic antibody with complement, however, abrogated the suppressor function, presumably by cytotoxicity. Anti-isotype with complement was ineffective. These findings suggest binding of ligand to a surface receptor of the suppressor M phi that although clearly not PC globulin, may be structurally similar to the PC idiotype. These receptors are retained in 3 day cultures of macrophages and are not removed by intensive washing. Ligand binding appears to modulate the suppressor function of M phi through blocking of the production of diffusible suppressor factor.

Animals↗
PubMed1982

Immunosuppression in plasmacytoma: induction of suppressor cells.

Immunosuppression in BALB/c mice with plasmacytomas (PC) is, at least in part, due to increased suppressor activity of splenic adherent cells. A PC subcellular fraction rich in intracisternal A particles, previously shown to have an immunosuppressive effect in normal BALB/c mice, is now shown to exert this effect through the development of splenic suppressor cells. The splenic suppressor cells induced with this subcellular fraction were found to be radioresistant adherent macrophages that suppressed the immune response of normal splenic cells to sheep erythrocytes through a diffusible factor, but did not influence their polyclonal IgM secretion ater LPS stimulation in vitro. These characteristics are identical to those of the naturally occurring suppressor macrophages in mice with PC. Whether the induction of suppressor cells is due to the intracisternal A particles themselves or a factor co-purified with them, remains to be established.

Animals↗
PubMed1983

Partial purification and properties of a murine plasmacytoma glucosyltransferase.

The enzyme UDP-glucose:dolichylphosphate glucosyltransferase has been purified 1700-fold from MOPC-315 plasmacytoma tissue. The purification combines differential detergent extraction of purified rough endoplasmic reticulum with subsequent ion exchange chromatography, dye affinity chromatography, and hydroxylapatite chromatography of the extract. The partially purified glucosyltransferase exhibits a Km of 0.79 microM for UDP-Glc and a Km of 0.65 microM for dolicholphosphate in the presence of 4 mg/ml of phosphatidylcholine. The reaction is dependent upon the addition of exogenous dolicholphosphate. The enzyme is activated by the choline containing lipids phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin. The dye Remazol blue acts as a competitive inhibitor of the enzyme with respect to UDP-Glc. The molecular weight of the enzyme has been determined to be approximately 37,000. The sole reaction product has been identified as dolichylphosphate glucose by isolation of the product by DEAE-cellulose chromatography and subsequent analysis of the acid-hydrolyzed product by both Bio-Gel P2 gel filtration and paper chromatography.

Animals↗
PubMed1978

Loss of oncogenicity and concomitant increased immunogenicity of murine plasmacytoma cell lines.

Murine plasmacytoma cells gradually decrease in oncogenicity with prolonged culture in vitro. Newly established cultures are oncogenic and cause lethal tumors. Subsequently, the cultures are oncogenic but some of the tumors regress. Later in the life of the culture none of the tumors are lethal. The longer the cells are in culture, the less oncogenic they become; eventually the cultures are nononcogenic in normal mice but do cause tumors in irradiated mice. Clones from the cultures vary from being very oncogenic to being nononcogenic. It appears that the nononcogenic cells have a selective growth advantage and become the dominant cell type in the cultures. Nononcogenic cultures are more effective for immunization to subsequent challenge with the original tumor than are the tumor cells or oncogenic cultures and may confer complete protection against lethal tumor challenge in adoptive transfer experiments. Mixtures of nononcogenic and oncogenic cells decrease the tumor-forming ability of the latter when they are injected together in one site or injected separately in two sites.

Animals↗
PubMed1984

Diffusible suppressor factor from splenic macrophages in murine plasmacytoma.

The immunosuppressive effect of splenic macrophages (M phi) in mice bearing plasmacytoma was previously shown to be mediated by a diffusible factor. This diffusible suppressor factor (DSF) was found to be non-dialysable and sensitive to heating to 56 degrees C and to the proteolytic action of trypsin. The suppressor factor could be removed from culture supernatants by binding to ligands that specifically bind to corresponding myeloma proteins. DSF from splenic suppressor M phi of mice bearing MOPC 315 was capable of binding dinitrophenyl L-lysine, and that from mice bearing MOPC 104E, dextran S. The suppressor factor apparently cross-reacted with anti-idiotypic antibody to the corresponding myeloma protein, but did not interact with anti-isotypic antibody to mouse immunoglobulins (Ig). A higher concentration of mouse Ig than that found in DSF preparations did not have a suppressive effect. Metabolic inhibitors for RNA and protein, but not DNA synthesis effectively blocked the production of DSF. These findings suggest that DSF is a non-Ig protein that may have a structural similarity to myeloma idiotype. Continuous RNA and protein synthesis is required for the elaboration of DSF by splenic suppressor M phi in cultures.

Animals↗
PubMed1978

Immunity against MOPC 104E plasmacytoma: effects of tumor size and time post therapy on in vivo tumor immunity.

BALB/c mice with the plasmacytoma MOPC 104E were cured of palpable tumors (6-15x10(7) cells) with a single injection of cyclophosphamide (10 mg/kg). Animals cured of tumor showed a considerable increase in their ability to reject secondary challenge with graded numbers of viable tumor cells. Mice with palpable subcutaneous tumors were cured therapeutically and rechallenged 22, 44, or 120 days post therapy. The ability of such animals to reject secondary tumor cell challenge was similar in all groups, which implied that in vivo tumor immunity remained relatively constant for at least 4 months post therapy. A second group of animals was treated therapeutically (10 mg cyclophosphamide/kg) 4, 11, or 20 days post tumor cell injection. These therapeutically treated animals were then rechallenged with various numbers of viable tumor cells 30 days post therapy. Mice given cyclophosphamide 4, 11, or 20 days post tumor injection rejected 6, 60, or 400 times as many tumor cells, respectively, as did control animals. These results implied that, over the range of tumor sizes investigated, exposure to greater amounts of tumor antigen resulted in increasing amounts of residual tumor immunity following cure.

Animals↗
PubMed1984

[A case of extramedullary plasmacytoma of the stomach].

A 51-year-old man with extramedullary plasmacytoma of the stomach is presented. He complained of epigastralgia. Barium meal revealed 2 submucosal tumors in the gastric body. Laboratory investigations showed neither hypergammaglobulinemia nor proteinuria. Bone X-ray examinations were not remarkable. There was tumor invasion to the pancreas and metastasis to the perigastric lymph nodes. Proximal gastrectomy was performed, and the patient died 5.5 years after the operation. Histologically, the proliferation of atypical plasma cells with eccentric nuclei was seen. Those cells invaded all layers of the stomach. The tumor cells were pyroninophilic and contained Russel bodies. Immunohistochemical study using the immunoperoxidase technique demonstrated IgG and lambda-light chains in the tumor cells.

Gastric Mucosa↗
PubMed1984

[An autopsy case of extramedullary plasmacytoma with systemic dissemination 2 years after the onset of a localized tumor in the nasal cavity].

A 73-year-old male was admitted because of a localized tumor in the nasal cavity, which was suspected to be malignant lymphoma by biopsy specimens. Laboratory findings were within normal limits except for small amounts of M protein (IgG-lambda) in the serum. The patient was successfully treated by radiotherapy, with the disappearance of both the tumor and M protein. Two years after the onset, however, a solid tumor was observed in the soft tissue, followed by rapid systemic dissemination. An increase in M protein was obvious, and the biopsy specimens disclosed plasmacytoma. The patient died three months after admission, and post-mortem examinations revealed a diffuse infiltration of plasmacytes predominantly in the soft tissues.

Aged↗
PubMed1981

The mode of action of splenic suppressor cells in murine plasmacytoma.

Polyclonal IgM secretion after LPS stimulation and antigen-dependent antibody production by splenic cells of BALB/c mice with plasmacytoma were found to be markedly reduced. The former occurred without mediation of suppressor cells, probably as the result of a quantitative reduction of mitogen-responsive B lymphocytes. On the other hand, the reduction in the generation of antibodies to sheep erythrocytes in vitro, as determined by the number of PFC, was found to be dependent on the activity of suppressor cells which had the functional characteristics of macrophages. The targets of these suppressor cells were found to be normal macrophages, B and T lymphocytes which were all independently suppressed. A diffusible factor appeared to be responsible for the suppressive effect of the suppressor macrophages interfering mainly with those early stages of the immune response involving antigen-triggered B cell activation.

Animals↗
PubMed1984

Inhibition of in vivo growth of murine plasmacytoma MOPC-460 by monoclonal anti-idiotypic antibodies directed at distinct idiotypes of the immunoglobulin on the surface of MOPC-460.

The effect of several well-characterized monoclonal anti-idiotypic antibodies on the in vivo growth of idiotype-bearing murine plasmacytoma cells was examined. They were chosen from a group of immunoglobulin G1 antibodies which react with the binding site determinants of M460, the immunoglobulin A dinitrophenyl-binding myeloma protein secreted by and present on the surface of MOPC-460, and included representatives of two families which recognize different determinants in the M460 variable region. The antibodies were administered daily, beginning 2 hr before i.v. tumor cell inoculation, and the effect on the appearance of tumor colony formation in the spleen was judged after 14 days. All four antibodies tested were inhibitory. At the highest doses used, the number of splenic tumor foci was reduced by up to 97%. The effect was highly specific since the growth of MOPC-315, which also produces an immunoglobulin A dinitrophenyl-binding myeloma protein, was unaffected by the antibodies, and a similarly prepared immunoglobulin G1 monoclonal antibody against an unrelated idiotype did not affect the growth of MOPC-460. The inhibition of tumor growth appears to be independent of complement and antibody-dependent cellular cytotoxicity mechanisms. A small fraction of clones escaping the antitumor effect of anti-idiotypic antibodies has stopped expressing the idiotype.

Animals↗
PubMed1984

[Clinical and diagnostic considerations on a case of pancreatic plasmacytoma].

An unusual case of obstructive jaundice due to metastatic pancreatic plasmacytoma is described. Initially post-transfusion hepatitis was suspected in the patient who suffered from multiple myeloma (IgA) and had received numerous transfusions for severe anemia. Clinical and laboratory findings indicated obstructive jaundice and the ecographic examination showed a dishomogeneous mass at the level of the pancreas. The investigators suggest that after this type of ecographic finding a percutaneous biopsy should be performed eliminating exploratory laparotomy, a high risk procedure in this type of patient, and eventually radiotherapy should be initiated since this type of tumor is radiosensitive.

Female↗
PubMed1984

Fusion of plasmacytoma and host cells in vivo: selection of proliferating and nonproliferating cultures.

The double-mutant cell line 4T00.1 is derived from a plasmacytoma of a BALB/c mouse and is resistant to 6-thioguanine and ouabain. These cells were inoculated into (BALB/c X C57BL)F1 mice by different routes--sc, ip, intrasplenically, and intrathymically. The degree of tumorigenicity and pattern of tumor development were site-dependent. Intrasplenic inoculation of 10(3)-10(4) 4T00.1 cells resulted in development of large omental tumors accompanied by marked ascites. Tenfold to a thousandfold more 4T00.1 cells were required to obtain tumors by other routes. From all solid tumors and ascites and from various organs of tumor-bearing mice, which were explanted into culture in double selective medium containing hypoxanthine, aminopterin, and thymidine plus ouabain (in which only hybrids between 4T00.1 and normal cells can survive), proliferating and nonproliferating cultures were obtained. Of the 14 proliferating cultures, 9 proved to be hybrids by chromosome and H-2 isoantigen analyses and were tumorigenic when 10(6) cells were inoculated sc into syngeneic F1 mice.

Animals↗
PubMed1984

Primary colonic plasmacytoma associated with acute myelogenous leukemia.

We present a case of primary colonic plasmacytoma associated with acute myelogenous leukemia in a 32-year-old man. The neoplastic plasma cells revealed monoclonal lambda-light chains in the cytoplasm using immunoperoxidase techniques. Histochemical and electron microscopic findings are described with a review of the literature.

Adult↗
PubMed1977

Murine plasma cells secreting more than one class of immunoglobulin heavy chain. II. SAMM 368--a plasmacytoma secreting IgG2b-kappa and IgA-kappa immunoglobulins which do not share idiotypic determinants.

SAMM 368 is a BALB/c plasmacytoma which secretes IgG2b-kappa and IgA-kappa paraproteins. Immunofluorescence studies of ascites cells from the tumor with purified, heavy chain class-specific antiglobulins demonstrate that single cells contain both IgG2 and IgA heavy chains. Idiotypic antisera prepared in mice and rabbits indicate that the two paraproteins produced by the tumor do not share idiotypic determinants. Analysis of the purified paraproteins for allotype markers showed that SAMM 368 IgA bears the BALB/c A12,13,14 determinants. SAMM 368 IgG2b does not carry any detectable allotypic determinants in spite of the fact that heterologous antisera identify the paraprotein as IgG2b.

Amino Acid Sequence↗
PubMed1984

Effect of TEPC-183 plasmacytoma on resistance of passively or actively immunized BALB/c mice to infection with Streptococcus pneumoniae.

This study focuses on the effect of TEPC-183 (tetramethylpentadecane)-induced plasmacytoma on resistance of mice to infection with Streptococcus pneumoniae type III. Vaccination of normal or of TEPC-183-bearing mice with either a polyvalent pneumococcal vaccine (Pnu-Imune) or purified polysaccharide type III protects both against challenge with live S. pneumoniae. However, a 38-fold increase in susceptibility of the tumor-bearing mice over that of controls was observed. Immunized splenectomized mice were ten times more susceptible to infection than were immunized normal mice. However, this increased susceptibility of splenectomized mice could be overcome by passively administered antibody. In passive protection experiments, antisera obtained from normal and TEPC-183-bearing or from cyclophosphamide-treated mice were almost equally protective. A 6-fold increase of antibody (133 ng of antibody), however, was required to protect TEPC-183-bearing mice against challenge with 500 organisms, as compared with the 22 ng of antibody required to protect normal mice, indicative of defective host defense mechanisms in addition to the lower production of antibody in the TEPC-183-bearing mice. In contrast, mice bearing an equal tumor load of Sarcoma 37 behaved similarly to normal mice, showing that the increased susceptibility to infection was due to TEPC-183, a particularly immunosuppressive tumor.

Animals↗
PubMed1980

Organization and complete sequence of identical embryonic and plasmacytoma kappa V-region genes.

We have determined the entire sequence of two immunoglobulin kappa variable region genes derived separately from embryonic and plasmacytoma cells. Both genes are in the germline configuration; both are organized into hydrophobic leader and mature V-region coding sequences separated by a short intervening sequence. Both are identical with one another throughout the 1360 bases determined. In addition, there is a simple repeat sequence of 31 CA doublets that occurs about 300 bases from the 3' side of the coding sequence in each gene.

Amino Acid Sequence↗
PubMedDate not supplied

[Translation of MOPC 21 plasmacytoma cell mRNA in a cell-free wheat germ system].

A wheat germ cell-free system was used for translation of kappa-chain IgG1 messenger RNA isolated from mouse plasmacytoma MOPC 21 cells polysomes. The system was optimised for a number of ingredients of the incubation mixture. Incorporation of labelled amino acids in polypeptides was shown as a function of K+, Mg2+, exogenous mRNA concentration and time, mRNA was purificated by two successive oligo (dT)-cellulose chromatographies and two successive sucrose gradient centrifugations or polyacrylamide gel electrophoresis. Different fractions of poly(A)-RNA stimulated protein synthesis 20--30-fold in a wheat germ cell-free system. Analysis of the translation product of 14 and 16S mRNA by SDS-polyacrylamide gel electrophoresis revealed polypeptide comigrating with the authentic L-chain IgG1 and specifically precipitating by an antiserum to mouse IgG and L-chain IgGl (MOPC 21). The 18 and 28S mRNA fractions directed the synthesis of polypeptides with molecular weight up to 50 000 dalton. Immunospecific translation product of the 18 and 28S mRNA contain both L- and H-chains.

Animals↗
PubMed1981

IgD-secreting murine plasmacytomas: identification and partial characterization of two IgD myeloma proteins.

We have used an immunofluorescence inhibition assay to identify 2 BALB/c plasmacytomas, TEPC-1017 and TEPC-1033, that secrete large quantitites of IgD. Both TEPC-1017 and TEPC-1033 myeloma proteins bound to anti-kappa as well as hybridoma and heterologous anti-delta antibodies, but not to anti-mu, gamma, alpha, or lambda antibodies. Both myeloma proteins were purified by (NH4)2SO4 precipitation, ion exchange chromatography, gel filtration, and Staphylococcus aureus Protein A absorption. These IgD kappa myeloma proteins were used to prepare affinity purified rabbit antibodies to delta-chain and the TEPC-1017 and TEPC-1033 idiotypes. Native TEPC-1017 and TEPC-1033 both had mobilities between those of mouse IgA kappa dimers and trimers when analyzed by polyacrylamide gradient gel electrophoresis. Both IgD myeloma proteins broke down under mild reducing conditions into subunits with electrophoretic mobilities slightly slower than those of an IgA kappa monomer. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of reduced TEPC-1017 and TEPC-1033 demonstrated kappa-chains and heavy chains that co-migrated with alpha chain. These data suggested that secreted IgD contains 2 delta 2 kappa 2 subunits that are linked by an easily reducible disulfide bond. The kappa-chains of IgD secreted by TEPC-1017 and TEPC-1033 have apparent m.w. of approximately 63,000 daltons, whereas the apparent m.w. of intracytoplasmic delta-chain, intracytoplasmic delta-chain synthesized in the presence of tunicamycin, and the cellfree translation product of TEPC-1017 delta-chain mRNA are 54,000, 43,000, and 44,000 daltons, respectively. This is compatible with the interpretation that the delta-chain peptide has a leader sequence and is N-glycosylated during or shortly after peptide synthesis and is glycosylated further shortly before IgD secretion.

Animals↗