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)

Human monoclonal antibodies produced by Epstein Barr (EB) virus transformation and/or cell fusion are frequently IgM antibodies which tend to cross react with a range of antigens and often bear little relationship to the highly specific IgG antibodies associated with human autoimmune disease. By fusing EB virus transformed B lymphocytes from a Hashimoto patient with a mouse myeloma line and selecting for synthesis of IgG class thyroglobulin (Tg) antibody, we have developed a hybridoma (VB/5) secreting Tg antibody of IgG2 subclass and lambda light chain type which has the characteristics of a monoclonal antibody on isoelectric focussing. The antibody has a high affinity for human Tg and recognises Tg from other primates but not non-primate Tg. However, it does not react with human thyroid peroxidase or a panel of other autoantigens. In terms of affinity constant, functional affinity and affinity heterogeneity, the antibody closely resembles the IgG2 lambda Tg antibody present in the serum of the Hashimoto patient whose B lymphocytes were used to develop the hybridoma. In addition to providing a useful reference standard for Tg antibody IgG subclass assays, VB/5 antibody and the hybridoma line provide a valuable starting point for detailed studies of Tg autoantibodies and the genes coding for the variable regions of their heavy and light chains.
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PMID:A human-mouse hybridoma which secretes monoclonal thyroglobulin autoantibody with properties similar to those of the donor patient's serum autoantibody. 256 81

Five human myeloma cell lines, KMM-1, KMS-5, KMS-11, KMS-12-PE, and KMS-12-BM, have been established at Kawasaki Medical School since 1980. As the KMS-12-PE and KMS-12-BM lines were obtained from the same patient, these five cell lines have been derived from four patients with multiple myeloma. The five myeloma cell lines are stably growing at present in RPMI 1640 medium supplemented with 10% fetal bovine serum. They can also grow in a defined culture medium without serum. That these cell lines were human myeloma cells was confirmed by the following findings. Ultrastructurally, all five cell lines showed features characteristic of plasma cells. KMM-1 and KMS-11 cells secreted lambda and kappa chains into the culture medium, respectively, but the other cell lines produced no immunoglobulins. KMM-1 expressed cytoplasmic lambda antigen, KMS-5 showed cytoplasmic delta, and KMS-11 expressed surface kappa, whereas KMS-12-PE and KMS-12-BM cells showed no surface or cytoplasmic immunoglobulins. Regarding reaction with a monoclonal plasma cell antibody (PCA-1), four of the five lines were positive, the exception being KMS-5. Another monoclonal antibody (CD38), which also recognizes plasma cells, responded to KMM-1, KMS-12-PE, and KSM-12-BM. KMS-5 cells expressed acute lymphoblastic leukemia antigens (CALLA). These data suggest that such lines as KMM-1, KMS-11, KMS-12-PE, and KMS-12-BM represent later stages of B-cell differentiation, and that KMS-5 represents a relatively early stage of B-cell differentiation. All the cell lines lacked Epstein-Barr virus nuclear antigen, showed abnormal karyotypes of human origin, and differed from each other in the isozyme patterns examined. Only KMS-5 was tumorigenic when transplanted subcutaneously into nude mice.
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PMID:Establishment of five human myeloma cell lines. 276 32

Stable cell lines producing monoclonal human antibodies can be derived by fusion of Epstein-Barr virus-transformed peripheral blood B lymphocytes (LCL) with the mouse myeloma line X63-Ag8.653. One major limitation to this approach is the establishment of LCL cultures with sufficient cells secreting the specific antibody. In this study on the production of anti-D(Rh) antibodies, the kinetics of the appearance of specific EBV-transformable precursors in the circulation was followed after secondary immunization, and the optimum time for obtaining B cells for the establishment of suitable LCLs was found to be during the period 2-4 weeks post boost. During this period the probability of obtaining LCLs suitable for fusion is significantly higher than from blood samples collected randomly. From these high-titre LCLs the success rate for the fusion process was high. The specific EBV target cells are presumably memory cells produced after the peak of the antibody response and having only a transient appearance in the circulation.
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PMID:Requirements for the establishment of heterohybridomas secreting monoclonal human antibody to rhesus (D) blood group antigen. 282 18

Peripheral blood B lymphocytes from a donor with positive tuberculin skin test reaction were transformed into lymphoblastoid cell lines by Epstein-Barr virus and then fused by polyethylene glycol with mouse myeloma cells. Human-mouse hybrid cells producing human IgM monoclonal antibody to purified protein derivative of tuberculin were isolated, and the concentrated supernatant of one of these cell hybrids was tested for the capacity of interfering with DNA synthesis of human and mouse lymphocytes. The hybrid cell supernatant was found to contain soluble factors that increased DNA synthesis in unstimulated human and mouse lymphocytes and that, conversely, decreased DNA synthesis in concanavalin-A-stimulated cells. Gel filtration experiments showed that these antagonistic activities were due to at least two different factors, one of which resembled human interleukin-1 in biochemical and biological properties.
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PMID:Interleukin-1-like activity produced by hybrids constructed with Epstein-Barr-virus-transformed human B lymphocytes and mouse myeloma cells. 282 40

Lymph node lymphocytes from patients with primary lung cancer were immortalized with Epstein-Barr virus, and culture supernatants were screened for cell-surface reactivity against allogeneic cancer cell lines. The percentage of wells containing detectable antibodies in initial screening ranged from 1 to 17%, but the vast majority of the cultures lost antibody activity on subsequent expansion. Two antibody-secreting clones, J309 and D579, derived from separate individuals and reactive with anaplastic lung cancer cell lines, were successfully expanded and fused with the NS-1 mouse myeloma cell line. The antibodies produced by these clones exhibited identical restricted serologic reactivity against cultured cell lines and detected a carbohydrate antigen present in the neutral glycolipid fraction of MCF-7 breast cancer cells. Serologic, immunochemical, and chemical analyses revealed that the antigen recognized by antibodies J309 and D579 is galactosylgloboside [Gal(beta 1----3)GalNAc(beta 1----3)Gal(alpha 1----4)Gal(beta 1----4)- GlcCer]. Conclusions regarding the significance of these findings with respect to the biology of lung cancer await further information concerning the distribution of galactosylgloboside in normal and malignant tissues and the frequency of antibodies to this structure in normal and tumor-bearing individuals.
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PMID:Recognition of galactosylgloboside by monoclonal antibodies derived from patients with primary lung cancer. 283 67

The fine specificity analysis of two human monoclonal antibodies (AbFCM1 and AbHJM1) reacting with gangliosides is described and their specificities are compared with analogous mouse monoclonal antibodies (mAbs). These two antibodies were generated from lymphocytes of melanoma patients by Epstein-Barr virus transformation followed by fusion with mouse myeloma NS-1. Using a wide variety of gangliosides, including N-glycolylneuraminic acid (NeuGc)-containing compounds, the precise structures recognized by these two antibodies were elucidated by enzyme-linked immunosorbent assay and immunostaining of thin-layer chromatograms. AbFCM1 reacted with N-acetylneuraminic acid (NeuAc)-type GM3, GD1a, sialylparagloboside, and GT1b in decreasing order of intensity. This antibody also reacted with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with NeuGc-type GM3, GM2, sialylparagloboside, (NeuGc)2-GD3 and -disialylparagloboside. The main epitope structures recognized by AbFCM1 are, therefore, NeuAc alpha 2----3Gal beta 1- and NeuAc alpha 2----8NeuGc alpha 2----Gal beta 1-. These results are similar to the specificity of mouse mAb M2590. AbHJM1 reacted with NeuAc-type GD3 and disialylparagloboside, GD2, GD1b, GM3, and GT1b, in decreasing order of intensity. Among NeuGc-type gangliosides, this antibody reacts with (NeuAc-NeuGc-)-GD3 and -disialylparagloboside, but did not react with gangliosides containing only NeuGc. Consequently the epitope structure recognized by AbHJM1 is probably (R)-(NeuAc alpha 2----8Sialic acid alpha 2----3)Gal beta 1-. Mouse anti-GD3 mAbR24, in contrast, showed strong reactivity only with GD3 and -disialylparagloboside among NeuAc-type gangliosides, but showed a similar pattern to AbHJM1 in its reactivity with NeuGc-containing gangliosides. Although these two human monoclonal antibodies are not highly restricted in their specificities, they reacted best with the major gangliosides, GM3 and GD3, present in the majority of human melanomas.
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PMID:Two human monoclonal antibodies reacting with the major gangliosides of human melanomas and comparison with corresponding mouse monoclonal antibodies. 290 45

Peripheral blood mononuclear cells from a patient with chronic myelogenous leukemia (CML), in remission, were depleted of CD8-positive T-cells and cultured with Epstein-Barr virus. Four of 20 cultures (20%) secreted human IgG antibodies selectively reactive with the cell surfaces of certain human leukemia cell lines. Three polyclonal, Epstein-Barr virus-transformed, B-cell lines were expanded and fused with the human-mouse myeloma analogue HMMA2.11TG/O. Antibody from secreting clones HL 1.2 (IgG1), HL 2.1 (IgG3), and HL 3.1 (IgG1) have been characterized. All three react with HL-60 (promyelocytic), RWLeu4 (CML promyelocytic), and U937 (monocytic), but not with KG-1 (myeloblastic) or K562 (CML erythroid). There is no reactivity with T-cell lines, Burkitt's cell lines, pre-B-leukemia cell lines, or an undifferentiated CML cell line, BV173. Leukemic cells from two of seven patients with acute myelogenous leukemia and one of five with acute lymphocytic leukemia react with all three antibodies. Normal lymphocytes, monocytes, polymorphonuclear cells, red blood cells, bone marrow cells, and platelets do not react. Samples from patients with other diverse hematopoietic malignancies showed no reactivity. Immunoprecipitations suggest that the reactive antigen(s) is a lactoperoxidase iodinatable series of cell surface proteins with molecular weights of 42,000-54,000 and a noniodinatable protein with a molecular weight of 82,000. Based on these data these human monoclonal antibodies appear to react with myelomonocytic leukemic cells and may detect a leukemia-specific antigen or a highly restricted differentiation antigen.
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PMID:Human monoclonal antibodies reactive with human myelomonocytic leukemia cells. 292 15

A myeloma cell line, MM.1, has been established from the peripheral blood cells of a patient with immunoglobulin A myeloma. MM.1 grows in suspension either singly or in small clusters and secretes lambda-light chain. Phenotypically, MM.1 cells lack most B cell antigens, but they do express human leukocyte antigen DR, PCA-1, and T9 and T10 antigens. Molecular analysis of MM.1 demonstrates that it is negative for the presence of the Epstein-Barr virus genome. Southern analysis of MM.1 detected a rearrangement of the lambda-light chain gene, and Northern analysis revealed high levels of lambda gene expression. Cytogenetic analysis of the MM.1 cell line revealed the presence of seven related chromosomally abnormal cell lines characterized by numerical and structural aberrations, and it revealed five nonclonal abnormal cells. The most notable abnormality is a reciprocal translocation involving band q24.3 of chromosome 12 and band q32.3 of chromosome 14; translocations involving 14q32 are frequently observed in neoplasms of B cell origin.
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PMID:Characterization of a novel myeloma cell line, MM.1. 292 41

Human cell lines established from cases of acute lymphoblastic leukemia, lymphosarcoma, Burkitt's lymphoma and multiple myeloma and representing stages of B-lymphocyte development ranging from pre-B through to plasma cells, were assessed for their ability to produce and respond to B-cell growth factors (BCGF). All B-cell lines studied were found to be constitutive producers of a growth activity which assisted the S-phase entry of normal activated B-cells and provided growth support for lymphoblastoid cells transformed by Epstein-Barr virus. Furthermore, all lines responded by enhanced proliferation to supernatants from a BCGF-producing T-cell hybridoma. Not all lines, however, displayed autostimulation to their own supernatants and no tumor B-cell line appeared totally dependent on soluble factors for its growth. Non-tumorigenic B-cell lines, by contrast, revealed a strict dependency on homologous growth factor for their continued proliferation in suspension culture. The findings support a progression model of lymphomagenesis based upon the utilization, production and, ultimately, emancipation from growth-promoting soluble factors.
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PMID:Capacity of B-lymphocytic lines of diverse tumor origin to produce and respond to B-cell growth factors: a progression model for B-cell lymphomagenesis. 298 45

Continuous cell lines have been established from spleen cells of patients with confirmed hairy cell leukemia (HCL). One cell line, HCL-Z1, lacks Epstein-Barr virus nuclear antigen (EBNA), grows attached to the substratum and retains typical features of hairy cells as revealed by transmission and scanning electron microscopy. HCL-Z1 differs morphologically from the three other EBNA-positive lymphoblastoid cell lines obtained (HCL-Z2, HCL-Z3, HCL-Z4) as well as from normal spleen cells or lymphocytes. The three lymphoblastoid cell lines derived from HCL patients show similar surface features as a line from a myeloma patient. Therefore, not all cell lines derived from HCL patients may be considered as representative of the patients leukemia cells.
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PMID:Establishment and characterization of an Epstein-Barr virus nuclear antigen-negative hairy cell line. 298 56


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