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)

Epstein-Barr virus (EBV) can induce a broad spectrum of hematological diseases, especially in immune deficient patients. We assayed for receptor for EBV (EBVR) using fluoresceinated viral particles on 44 human hematopoietic cell lines derived from patients with T, B, and non-T, non-B acute lymphocytic leukemia (ALL), non-lymphoid leukemia, Burkitt lymphoma, myeloma and several unique lines we and others have recently developed. All 31 EBV nuclear-associated antigen (EBNA) negative cell lines were of neoplastic origin. Seven of 13 EBNA-positive cell lines were of normal cell origin. Four of 25 non-B (surface immunoglobulin negative) EBNA-negative neoplastic cell lines were EBVR-positive. Three of six EBNA-negative B-cell (surface immunoglobulin positive) lines were EBVR-positive. Nine of 13 EBNA-positive Burkitt and non-Burkitt cell lines strongly expressed EBVR. Four EBNA-positive Burkitt lymphoma cell lines exhibited EBVR only to a limited degree. Studies of the cell lines for EBVR, complement receptors (CR) and surface immunoglobulin (SIg) revealed that presence of SIg does not obligate the presence of EBVR. Functional EBVR accompanied SIg among EBNA-negative cell lines. SIg-negative cell lines can possess EBVR. Fourteen of 16 EBVR-positive lines were also positive for CR. The EBVR assay is a useful tool for assessing the potential role of EBV in the induction of hematopoietic disorders.
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PMID:Catalogue of Epstein-Barr virus (EBV) receptors on human malignant and non-malignant hematopoietic cell lines. 298 80

Multiple myeloma patients are deficient in normal polyclonal serum immunoglobulins. To determine the reasons for this decrease, we quantitated and compared the number of surface IgM+ B lymphocytes, and the number of B cells susceptible to transformation by Epstein-Barr virus (EBV) with the concentration of IgM in serum. Serum IgM levels varied considerably in individual patients, temporally shifting from undetectable to normal amounts and then dropping again to undetectable levels. A transient rise to normal serum IgM concentrations was seen in 42% of patients assessed at two or more time points. Of 44 patients, 52% showed a lack of correlation between the number of surface IgM+ (sIgM+) B cells and serum IgM concentration. One subset of patients (25%) had detectable to normal numbers of sIgM+ B cells in blood but undetectable levels of serum IgM. Transformation of B cells from these patients indicated a block in IgM secretion that was extrinsic to the B cells that were fully able to transcribe, translate, and secrete IgM after EBV transformation. A second subset of patients (27%) had undetectable numbers of sIgM+ B cells but near normal levels of serum IgM, suggesting abundant secretion by few clones of B cells. Of 18 patients with monoclonal gammopathy of undetermined significance (MGUS), 26% showed a lack of correlation between the numbers of sIgM+ B cells and serum IgM concentration. We suggest that in patients with multiple myeloma, and in some with MGUS, there exists a mechanism(s) extrinsic to the B cell that mediates an arrest in terminal B lymphocyte maturation.
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PMID:Abnormal function of B lymphocytes from peripheral blood of multiple myeloma patients. Lack of correlation between the number of cells potentially able to secrete immunoglobulin M and serum immunoglobulin M levels. 298 39

A variety of types of human B-cell lines were evaluated for their ability to produce interleukin 1 (IL-1)-like factors. All of the eight Epstein-Barr virus (EBV)-transformed B lymphocyte lines, three of four of the EBV+ lymphoma lines, only three of seven of the EBV- lymphoma lines, and none of the three tested myeloma lines secreted some IL-1 activity. The IL-1-like factor produced by the cell lines was detected on the basis of its thymocyte comitogenic and/or fibroblast proliferative activities. Injections of partially purified IL-1-like factor from one of the EBV-transformed B-lymphocyte lines also induced the appearance of an acute phase protein (haptoglobin) in the serum of C3H/HeJ mice. These biological activities are identical with those of monocyte-derived IL-1. Thymocyte comitogenic activity and fibroblast proliferation activity from one of the EBV-B cell line-derived IL-1-like activities were not dissociable by biochemical procedures, including HPLC gel filtration and HPLC anion-exchange chromatography. However, the IL-1-like factor from one of the EBV-B lymphocyte cell lines was larger in size (25 kDa) and more acidic (pI 5.5) than monocyte-derived IL-1.
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PMID:B-cell-derived interleukin-1 (IL-1)-like factor. II. Sources, effects, and biochemical properties. 299 9

The specificity repertoire of B lymphocytes from 14 multiple myeloma patients has been studied using the technique of Epstein-Barr virus (EBV) transformation of peripheral blood lymphocytes (PBL) coupled with clonal analysis by limiting dilution. We find that up to 100% of the B cells from myeloma patients undergoing EBV transformation secrete IgM specific for determinants on the F(ab')2 region of autologous and/or heterologous monoclonal immunoglobulin. In normal individuals 0.02-0.73% of the transformed B cells secrete IgM specific for F(ab')2 determinants. Two patients with monoclonal gammopathy of undetermined significance had only a weak reactivity to F(ab')2 fragments. The number of anti-F(ab')2 B cells was up to 145-fold greater in patients than in normal donors. The majority of antibodies from patient clones recognized determinants shared among 3-12 different F(ab')2 fragments, whereas those originating from normal donor B cells saw determinants expressed on only one or two of the panel of test F(ab')2 fragments. There was a preference for autologous M components and a high proportion of antiidiotypic reactivity in five of eight patients so analyzed. We speculate that these findings indicate the existence of an anti-F(ab')2 immunoregulatory network mediating patient immunodeficiency network mediating patient immunodeficiency, thereby creating an abnormality that may enable the progression of multiple myeloma.
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PMID:Specificity repertoire of lymphocytes from multiple myeloma patients. I. High frequency of B cells specific for idiotypic and F(ab')2-region determinants on immunoglobulin. 299 34

We have previously described the derivation of a monoclonal antibody, S2C6, to a novel 50 Kdalton antigen associated with human urinary bladder carcinoma. No reactions were obtained with carcinomas of unrelated origin or with normal urothelial cells. However, the antibody also reacted with a similar antigen on some cell lines of B lymphocyte origin. Using large panels of target cells we have now shown that this reactivity was entirely restricted to cells of the B lineage within the haematopoietic system. As opposed to its apparent restriction to malignant cells of the urothelium, the S2C6 antigen was expressed by normal B lymphocytes as well as by many malignant B cells (chronic lymphocytic leukaemia, hairy cell leukaemia and immunocytoma). Pre-B cells derived from acute lymphocytic leukaemia and plasma cells from multiple myeloma lacked the antigen. Expression was significantly enhanced on cultured B cells from Burkitt lymphomas and on Epstein-Barr virus-transformed lymphoblastoid cell lines including those of the pre-B phenotype derived from fetal bone marrow. As judged from the molecular size and the distribution pattern displayed by the S2C6 antigen it appears to be distinct from other B cell antigens previously described. A possible relation of the S2C6 antigen to a receptor for B cell growth factors is discussed.
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PMID:A p50 surface antigen restricted to human urinary bladder carcinomas and B lymphocytes. 299 89

Antigen-specific human monoclonal antibodies (hMoAb) were investigated with particular emphasis on the stability and scale-up of production. Peripheral blood lymphocytes from a healthy donor previously vaccinated with tetanus toxoid (TT) were resensitized in vitro with the antigen in the presence of pokeweed mitogen (PWM). Three days after the stimulation, lymphocytes were infected with Epstein-Barr (EB) virus. Among EB virus transformants, several lymphoblastoid cell clones producing anti-TT hMoAb were established. One of these clones, 3G6, produced about 10 micrograms/ml of IgM (K) in the culture supernatant. Furthermore, 3G6 cells were fused with murine myeloma cells (X63-Ag8 X 653) and three heterogeneous hybridoma clones (HE719, HE810 and HE811) were obtained after careful hybrid selection in hypoxanthine-aminopterin-thymidine-ouabain containing medium and cloning by limiting dilution technique. These hybrid clones contained human HLA and mouse H-2d antigens together with mouse-human mixed karyotype. When these mouse-human hybridomas were injected i.p. into pristane-treated nude mice of BALB/c origin, ascites were found and a large amount of anti-TT hMoAb up to 0.5 mg/ml were produced there. These hybridomas have retained their anti-TT antibody-producing capabilities over 10 months. The approach described here has a potential application for the production of other antigen-specific hMoAb.
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PMID:Characterization of stable Epstein-Barr (EB) virus transformed cell lines and mouse-human hybridomas producing a large quantity of anti-tetanus toxoid (TT) monoclonal antibody. 300 6

A method of producing human monoclonal antibody by combining somatic cell hybridization technology with the capability of Epstein-Barr virus (EBV) to transform human B lymphocytes is described. Peripheral blood lymphocytes from a donor with positive tuberculin skin test reaction were transformed by EBV and then tested for antibody production to mycobacterial purified protein derivative (PPD) by an enzyme-linked immunosorbent assay. Two EBV-transformed lymphoblastoid cell lines making IgM antibodies to PPD were obtained. One of these cell lines was fused by polyethylene glycol with a murine hypoxanthine-guanine phosphoribosyl transferase-deficient myeloma cell line that had been selected for resistance to ouabain. The human-mouse hybrids were selected in ouabain-containing HAT medium and 11 heterohybridomas producing IgM antibody to PPD were obtained. One of these was cloned by limiting dilution with efficiency at least 20-fold higher than parent EBV-transformed cell line. Heterohybridoma subclones reached levels of IgM antibody as high as 75.0 micrograms/ml of culture medium, whereas IgM production of EBV-transformed B cell clones ranged between 3.0 and 4.0 micrograms/ml.
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PMID:Human monoclonal antibody to purified protein derivative of tuberculin produced by hybrids constructed with Epstein-Barr virus-transformed B lymphocytes and mouse myeloma cells. 300 5

Patients with multiple myeloma are generally immunodeficient, with pronounced depression in primary antibody responses. We have attempted to delineate the reasons for the humoral immunodeficiency by analyzing the specificity repertoire of the surface immunoglobulin (Ig)-positive B cells in patients with multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS), in comparison with normal donors. B lymphocytes from 26 patients with multiple myeloma, 12 patients with MGUS, and 8 normal donors were transformed with Epstein-Barr virus (EBV) and cultured at limiting dilution for clonal analysis. The Ig secreted by each clone was analyzed for class and anti-tetanus toxoid (TT) specificity to determine the frequencies of IgM, IgG, anti-TT IgM, and anti-TT IgG antibody-secreting clones. Our objective was to establish whether the inability to mount humoral responses to common environmental pathogens was due to a lack of specific B cells or to inhibition of B-cell function. Our results indicate that the quantitative B-cell deficiency in patients was due to a nonrandom loss of selected sets of B cells. Although most patients had a reduced aggregate number of B cells, the number of TT-specific B cells was normal. There was, on average, a threefold increase in the proportion of the B-cell specificity repertoire devoted to recognition of TT. Forty-four percent of the patients with MGUS were also affected. In addition, the TT-specific B cells in multiple myeloma patients were severely compromised in their ability to secrete antibody or to differentiate to antibody-secreting cells in vivo. This arrest in differentiation appears to be extrinsic to the B cells, as they were fully able to secrete anti-TT antibody after transformation and culture in vitro. We postulate the existence of an autoimmune inhibitory network mediating the arrest in B-cell differentiation and the humoral immune deficiency.
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PMID:Humoral immune deficiency in multiple myeloma patients due to compromised B-cell function. 302 34

The mouse myeloma X63-Ag8.653 was fused to peripheral blood lymphocytes (PBL) from apparently healthy individuals, autoimmune patients and volunteers immunised with Rhesus (D) positive erythrocytes. Fusions were performed with or without prior transformation of PBL with Epstein-Barr virus (EBV). Using untransformed PBL, under the best conditions a mean fusion frequency of 8.4 X 10(-6) was obtained, with 22% of the resulting hybridomas secreting human immunoglobulin. Fusions with EBV-transformed cells gave fusion frequencies of 1.0 X 10(-4), with 85-90% of hybridomas secreting human immunoglobulin. The heterohybridomas formed in both cases cloned efficiently and had doubling times of 24-30 h. The heterohybridomas secreted human IgM, IgG and IgA of both kappa and lambda isotypes and culture supernatants contained up to 50 micrograms ml-1 of human immunoglobulin. Mouse immunoglobulin was not detected in the culture supernatants. 28 hybrids were selected for vigorous growth and antibody production by repeated cloning. Immunoglobulin synthesis was stabilised in 26 of these hybridomas after two or three cloning steps. The heterohybridomas have been successfully grown in large volumes for periods up to 15 months. It is concluded that the mouse myeloma X63-Ag8.653 is a suitable fusion partner with EBV-transformed B cells in the efficient production of human monoclonal antibodies.
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PMID:The efficient production of stable, human monoclonal antibody-secreting hybridomas from EBV-transformed lymphocytes using the mouse myeloma X63-Ag8.653 as a fusion partner. 302 93

A mouse monoclonal antibody named BU11 which detects an antigen strongly expressed on human plasma cells is described. The antibody stains plasma cells in tonsil sections, fresh and cultured plasmacytoid cells from the bone marrow of patients with multiple myeloma and cells of the plasmacytoid cell line RPMI 8226 used as the immunogen. In vitro studies of pokeweed mitogen (PWM) stimulated peripheral blood B cells and Epstein-Barr virus (EBV) stimulated tonsil B cells show that the antigen is present mainly on cells coexpressing the OKT10 antigen and containing cytoplasmic immunoglobulin (cIg). The BU11 antigen is expressed weakly on some normal B cells and is not present on T cells, monocytes or granulocytes. The antigen is of molecular weight 58kD under reducing conditions and is biochemically distinct from previously described plasma cell antigens.
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PMID:An antigenic study of human plasma cells in normal tissue and in myeloma: identification of a novel plasma cell associated antigen. 302 83


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