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)

Groups of BALB/c mice were treated with various conjugates of 2,4 dinitrophenyl (DNP) and BALB/c myeloma proteins belonging to the four subclasses of IgG (IgG1, IgG2, IgG2b, IgG3). Immediately therafter, they were challenged with DNP-keyhole limpet hemocyanin in complete Freund's adjuvant and antibody to the hapten was measured by direct and indirect hemolytic plaque assay. The results show that all subclasses of IgG are effective as tolerance-inducing carriers. However, the ability of induce tolerance is dependent upon the concentration of hapten bound to each myeloma protein. Tolerogenic conjugates suppress both direct and indirect plaque-forming cells in all types of antibodies measured (IgG1, IgG2a, IgG2b, IgGa), whereas, non-tolerogenic conjugate failed to suppress them. The intact molecule of IgG but not its fragments (Fab, F(ab)2', Fc) appear necessary as tolerance-inducing carriers. It is suggested that the ability to induce tolerance is related to the capacity of the tolerogenic conjugates to cause receptor blockade.
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PMID:Carrier determined tolerance with various subclasses of murine myeloma IgG. 76 77

A modification of the hemolytic plaque assay using protein A-coated red cells is described which makes use of the fact that the Fc portion of IgG binds to protein A. A number of murine plasmacytomas secreting different classes of Ig have been tested for plaque formation with these indicator red cells. In the presence of complement-binding antibodies specific for the corresponding class of secreted Ig, between 10 and 70% of all plated myeloma cells formed plaques. The assay shows a prozone effect in excess of antibody, suggesting that complexes of antibody and secreted Ig effect lysis of the target cells. This assay can be used to enumerate cells secreting any molecules for which complement-binding antibodies are available.
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PMID:A plaque assay for all cells secreting Ig of a given type or class. 78 96

The defects in two nonsecreting variant clones of the mouse plasmacytoma MOPC 21 (P3) were studied by tissue culture methods. The variants (NSI and NSIII) do not synthesize detectable heavy chains. NSI synthesizes, but does not secrete, light chains and NSIII does not synthesize light chain. A screening procedure was used allowing the detection of revertant cells secreting immunoglobulin. The method is based on a hemolytic plaque assay using anti-immunoglobulin-coated red cells. No revertants were detected among 2 x 10(7) cells. Both variant lines were fused to another myeloma line (PI) which secretes a complete immunoglobulin and excess light chains. Analysis of the products by isoelectric focusing showed that in the hybrids there was no reactivation of synthesis of the nonexpressed chains. The defects leading to loss of synthesis cannot therefore be complemented in the hybrid lines. The secretion of light chain in NSI, on the other hand, could be complemented in the hybrid but the light chain was only secreted as part of a new immunoglobulin hybrid molecule.
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PMID:Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines. 82 74

Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody-producing cells. The hybrid lines derived are permanently adapted to grow in tissue culture and are capable of inducing antibody-producing tumors in mice. Spleens from mice immunized against sheep red blood cells (SRBC) were fused to an 8-azaguanine-resistant clone (X63-Ag8) of MOPC 21 myeloma. Over 50% of the derived hybrid lines produce and secrete immunoglobulins different from the MOPC 21 myeloma. About 10% of the hybrid lines exhibit anti-SRBC activity. The high proportion of antibody-producing hybrids suggests that the fusion involves a restricted fraction of the spleen cell population, probably cells committed to antibody production. In order to avoid the presence of the MOPC 21 heavy chain in the specific hybrids, another myeloma cell line (NSI/1-Ag4-1) has been used. This is a nonsecreting variant of the MOPC 21 myeloma which does not express heavy chains. Three anti-SRBC (probably of the mu, gamma2b and gamma1 classes, respectively) and two anti-2,4,6-trinitrophenyl (of the mu class) antibody-producing hybrids have been repeatedly cloned. By random selection and by selection of specific clones according to their lytic activity (clone plaque selection), a number of different lines have been constructed. Such lines express different combinations of the four possible chains of each hybrid line: the myeloma gamma and K chains and the specific antibody heavy and light chains. In three cases (Sp1, Sp2 and Sp7) it is shown that only the specific H and L combination has activity and that the myeloma chains are unable to substitute for them. In most cases lines have been derived which no longer express the MOPC 21 chains but only the specific antibody chains.
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PMID:Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion. 82 77

The anti-phosphorylcholine (PC) antibodies synthesized by BALB/c spleen cells in microcultures upon immunization with heat-killed vaccine of Pneumococci R36A (Pn) are directed exclusively to the PC epitope. These antibodies are of very restricted avidity and 88% of the responding clones express the idiotype characteristic of the TEPC-15 PC-binding myeloma. This idiotypic restriction appears to be due to the absence of clones capable of expressing other idiotypes, rather than to "clonal dominance". The estimated frequency of precursor cells for the PC epitope is 1 X 10(-5) to 2.5 X 10(-5). These precursors give rise to clones with an average size of 9 plaque-forming cells. When the logarithm of the number of negative wells was plotted against the number of spleen cells/well, the fraction of nonresponding cultures decreased exponentially as the number of spleen cells was increased. This indicated that only one cell type was limiting in our assay, presumably a B cell. Furthermore, treatment of spleen cells with AKR anti serum completely abolished the response to sheep red cells without affecting the response to PC. It is concluded that PC is a T cell-independent antigen. Of interest was the finding that PC requires adherent (A) cells and this is a particular characteristic of PC, since most T cell-independent antigens have been found not to require A cells. Reasons for the possible homogeneity of the response to PC are also discussed.
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PMID:Antibody response to phosphorylcholine in vitro. I. Studies on the frequency of precursor cells, average clone size and cellular cooperation. 108 36

The effect of tumor growth on serum immunoglobulin levels and on the immune response to sheep erythrocytes (SRBC) was studied in BALB/c mice bearing MOPC-315 (IgA), MOPC-460 (IgA), MOPC-173 (IgG2a) and MOPC-104E (IgM) to gain insight into the immunologic competence of the plasmacytoma-bearing host. The initial increase of myeloma protein coincided with the first appearance of the tumor and increased as the tumor progressed. However, at the time of death there was little correlation between spleen weights, tumor size, and myeloma-protein levels. The mean serum concentration of the myeloma proteins reached a higher level in the mice bearing tumors transplanted i.p. compared to those with tumors transferred subcutaneously (s.c.). Non-myeloma immunoglobulin levels in the serum were reduced: IgM was significantly lowered in the presence of MOPC-315 injected i.p. and MOPC-460 injected s.c. and the IgG2 levels were depressed in mice injected i.p. with MOPC-315 and MOPC-104E. The only significant reduction of IgA levels was seen when MOPC-173 was transplanted i.p. The decreases observed in immunoglobulin levels correlated with plasmacytoma growth. They were specific for myeloma and were not due to tumor growth per se since the levels of all immunoglobulins tested increased in the presence of Sarcoma 37, a pleomorphic neoplasm. The primary plaque-forming cell (PFC) response of tumor-bearing animals after the injection of 0.5 ml of 10% SRBC was either similar or enhanced compared to the controls. However, with a lower SRBC dosage (0.5 ml of 2% SRBC) the indirect PFC were reduced with mice bearing MOPC-104E and MOPC-173. Tumor sizes did not seem to correlate with reduction of the PFC response. MOPC-460-bearing mice had a comparable number of PFC per spleen to those of the controls, but reduced numbers when calculated per 10 spleen cells. Consistently, hemagglutination titers were reduced in all tumor-bearing animals. The number of direct and indirect PFC per spleen was increased in mice bearing Sarcoma 37, compared to the controls. The possible implications of these findings are discussed.
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PMID:The effect of plasmacytomas on serum immunoglobulin levels of BALB/c mice. 108 19

IgA protease is a proteolytic enzyme found in whole human saliva and in dental plaque that cleaves both secretory and myeloma IgA of human origin to yield intact Fabalpha and Fcalpha fragments. To determine which bacteria are capable of producing this enzyme, we have examined a variety of strains normally found in the human oral cavity and a number of streptococci of known Lancefield group serotype. Streptococci of groups A, B, C, D, F, G, H, M, and N, Streptococcus mutans, Streptococcus sanguis, Streptococcus mitior, Streptococcus salivarius, Streptococcus faecalis, Veillonella, Lactobacillus, Actinomyces, Propionibacterium, Bacteroides, and Fusobacterium were grown in liquid medium, and fluids were examined for IgA protease activity. Only S. sanguis and clinically isolated group H streptococci elaborated IgA protease under the culture conditions used. Negative strains could not be stimulated to produce the enzyme when cultured in the presence of secretory IgA. Among the natural oral bacteria, capacity to produce IgA protease is restricted to certain species of Streptococcus, notably those of the group H serotype. Since secretory immunity is mediated by the IgA class of antibody, the presence of this enzyme at mucosal surfaces could modify the secretory immune function.
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PMID:Evaluation of human oral organisms and pathogenic Streptococcus for production of IgA protease. 116 76

Hybridomas secreting monoclonal (MAB) to transmissible gastroenteritis virus (TGEV) were produced by fusion of SP2/0 myeloma cells and splenic lymphocytes of BALB/c mice immunized with the virulent cell-passaged Miller strain of TGEV. The MAB secreted by these hybridomas were partially characterized; 4 of them (MA4, MA5, MH11, MB2) had high-neutralization titer for TGEV. The remaining 7 (MC6, MD9, ME5, MG5, MF2, ME9, MG7) did not neutralize TGEV at 1:25 dilution. All 4 neutralizing and 2 of the nonneutralizing MAB reacted with the E2 protein of TGEV in a radioimmunoprecipitation assay. The remaining 5 MAB reacted with the E1 protein of TGEV. Reactivity of the MAB was tested in an indirect immunofluorescent assay with 3 cell culture-adapted strains of TGEV (Miller, Purdue, and Illinois) and 13 wild-type isolates of TGEV. Neutralizing MAB reacted with all 13 wild-type isolates and the 3 cell culture-adapted strains of TGEV. In contrast, nonneutralizing MAB that reacted with the Miller strain of TGEV varied in their reactivity with the wild-type TGEV isolates. Reactivity of neutralizing MAB was also tested, using plaque-reduction neutralization assays with Miller, Purdue, and Illinois strains and 5 wild-type isolates. All 4 neutralizing MAB neutralized the 8 virus isolates, but the neutralization titer was higher with the homologous virus than with the heterologous virus isolates. However, neutralization titers of the 4 neutralizing MAB were 4 to 16 times higher for the homologous Miller strain of TGEV than for the heterologous Illinois and Purdue strains, and were 4 to 1,000 times higher than for the wild-type isolates.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization and reactivity of monoclonal antibodies to the Miller strain of transmissible gastroenteritis virus of swine. 168 28

A diagnosis of nonsecretory myeloma was established in two patients with anemia and proteinuria on the basis of the suppression of polyclonal immunoglobulins and the increase of plasma cells in the bone marrow. No paraprotein was detected in the serum or concentrated urine of these patients. However, a plaque-forming assay of bone marrow cells showed the secretion of monoclonal immunoglobulin by the myeloma cells. Moreover, renal biopsies from both patients indicated the deposition of monoclonal light chains in the glomerular mesangium and basement membrane, as well as in the tubular basement membrane, a pattern consistent with light-chain deposition disease. These observations suggested that the secreted paraprotein disappeared rapidly as a result of enhanced catabolism or deposition in organs such as the kidney, producing severe proteinuria and chronic renal failure. The plaque-forming assay is a useful technique for the demonstration of this type of nonsecretory myeloma, pseudo-nonsecretory myeloma.
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PMID:Pseudo-nonsecretory multiple myeloma with light chain deposition disease. 190 81

Two hybridomas producing monoclonal antibodies reactive with natural killer cells were selected after fusion of 129 anti-C57BL/6 immune spleen cells with P3X63-Ag8.653 myeloma cells. Treatment of normal or stimulated cells with the 4LO3311 or the 4LO439 mAb and rabbit complement inhibited natural killer and antibody-dependent cellular cytotoxicities, whereas cell lysis mediated by natural cytotoxic cells, cytotoxic T lymphocytes, or activated macrophages was unaffected. Lymphokine-activated killer activity was reduced after complement-mediated treatment of interleukin-2-stimulated spleen cells with the 4LO3311 mAb but not after treatment with the 4LO439 mAb. Similar treatment of spleen cells with either mAb had no effect on the mitogen-induced proliferation of T and B lymphocytes and did not alter the frequency of antibody plaque-forming cells in immune spleen cell suspensions. The 4LO3311 and 4LO439 mAbs thus appear to be specific for NK cells and their progeny. Flow cytometry analysis confirmed that 4LO3311+ and 4LO439+ cells are phenotypically identical to NK-1.1+ cells. The epitope recognized by the 4LO3311 mAb has the same strain distribution as the NK-2.1 alloantigen previously detected with NZB anti-BALB/c antiserum, whereas the 4LO439 mAb appears to identify a new NK cell marker exclusively expressed in mice of C57BL lineage. The relationship of the molecules detected with either the 4LO3311 or the 4LO439 mAb to polymorphic antigens of the Ly series is discussed.
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PMID:Identification of murine natural killer cell subsets with monoclonal antibodies derived from 129 anti-C57BL/6 immune spleen cells. 201 2


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