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)

The production of anti-idiotypic antibodies from Epstein-Barr virus transformed peripheral blood lymphocytes was analysed in 12 patients with multiple myeloma and monoclonal gammopathy of undetermined significance. A low anti-idiotype production was found in patients with advanced disease (multiple myeloma stage III), whereas the production was high in patients with multiple myeloma stage I and monoclonal gammopathy of undetermined significance (MGUS) (P less than 0.01). The study supports the existence of an immunological network response in patients with monoclonal gammopathies.
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PMID:Anti-idiotypic antibodies in patients with monoclonal gammopathies: relation to the tumour load. 204 84

Four human myeloma cell lines (MM-S1, MM-A1, MM-Y1 and MM-C1) were established from patients in the terminal stage of multiple myeloma. All the cell lines were PCA-1 positive and three were CD38 (OKT10) positive. The class of cytoplasmic immunoglobulin in each of these cell lines was identical to that of the monoclonal protein detected in each patient. Epstein-Barr virus nuclear antigen was negative in all cell lines. An examination of the tritiated thymidine uptake showed that all four cell lines proliferated in response to interleukin-6 (IL-6), while MM-S1 also responded to IL-5. Immunological staining with an anti-IL-6 receptor monoclonal antibody revealed the presence of receptors for IL-6 on the cells from each cell line. Three of them formed colonies dependent on IL-6 in methylcellulose semi-solid culture. All four cell lines grew better when human plasma was added as a supplement to the culture in comparison to fetal calf serum. Northern blot analysis showed that the three cell lines tested did not express IL-6 messenger RNA. These results indicate that these four cell lines are responsive to IL-6, but not by an autocrine mechanism, at least in the three lines examined.
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PMID:Establishment and characterization of four myeloma cell lines which are responsive to interleukin-6 for their growth. 207 43

A human monoclonal autoantibody to thyroglobulin (Tg) of subclass IgG2 was developed by fusing a mouse myeloma with Tg antibody secreting Epstein-Barr virus (EBV)-infected B lymphocytes from a Hashimoto patient. Subsequent studies showed that EBV-infected B lymphocytes from this patient synthesized IgG2 Tg antibody while unfractionated blood lymphocytes cultured with pokeweed mitogen secreted IgG1, IgG2, and IgG4 Tg antibodies in amounts proportional to those present in the patient's serum. To investigate this discrepancy further, we cultured EBV-infected lymphocytes from blood, lymph nodes, and thyroid tissue in medium alone and with increasing concentrations of PHA. In individuals with thyroid autoantibodies predominantly of subclass IgG1, PHA enhanced the levels of total Tg antibody synthesis without affecting the IgG subclass distribution. However, in patients with serum autoantibodies of subclasses IgG1, 2, and 4, the increased levels of total Tg antibody synthesis were associated with increased amounts of thyroid autoantibodies of all of these subclasses; in some instances IgG1 and IgG4 autoantibodies were only synthesized in cultures containing PHA. These observations suggest that addition of the T-cell mitogen PHA to cultures of EBV-infected lymphocytes may ensure activation of B-cell precursors committed to synthesizing the IgG subclasses characteristic of serum antibody in the lymphocyte donor. Since Tg antibodies of subclasses IgG2 and IgG4 recognize different epitopes on Tg, the ability to produce human monoclonal antibodies of different IgG subclasses may simultaneously ensure the development of antibodies to different epitopes on the same antigen.
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PMID:Potential role of PHA in producing human monoclonal thyroid autoantibodies of different subclasses. 210 61

GM2 ganglioside is a common cell surface constituent of human melanoma and other tumors of neuroectodermal origin, and vaccination with GM2 ganglioside results in high levels of anti-GM2 antibodies in patients with melanoma. Lymphocytes from a GM2-vaccinated patient (VS) were transformed by Epstein-Barr virus and tested for production of antibodies with reactivity for GM2-positive tumor cells. A high percentage of antibody-producing B cells was detected, but antibody reactivity was generally lost during culture expansion. Two cultures, however, remained stable for antibody productivity and one was used to develop a stable hybrid line with mouse myeloma. The monoclonal antibody (designated 3-207) derived from patient VS has dual specificity for GM2 and GD2, despite the fact that only GM2 antibody could be detected in the patient's serum. Monoclonal antibody 3-207 shows high-titered reactivity with a range of melanoma, astrocytoma, neuroblastoma, and leukemia cell lines, cells with prominent cell surface expression of GM2 and GD2. The cell surface reactivity of monoclonal antibody 3-207 was not abolished by treatment of target cells with neuraminidase, as the enzyme converted GD2 to GM2, which was still detected by monoclonal antibody 3-207.
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PMID:Human monoclonal antibody with dual GM2/GD2 specificity derived from an immunized melanoma patient. 215 45

A patient with chronic myeloid leukemia secreted an antibody to blood group glycosyltransferases after ABO-incompatible bone marrow transplantation (B recipient/O donor). Peripheral B lymphocytes from the recipient were transformed with Epstein-Barr virus, and then fused by polyethylene glycol with mouse myeloma cell line P3-X63/Ag8.653. After the cloning of the hybridoma cells, a cell line which produced human IgM antibody to blood group glycosyltransferases was established. The antibody completely neutralized B transferase activity at low concentration, while a larger amount of immunoglobulins was required to neutralize A transferase activity.
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PMID:Monoclonal antibody to blood group glycosyltransferases, produced by hybrids constructed with Epstein-Barr-virus-transformed B lymphocytes from a patient with ABO-incompatible bone marrow transplant and mouse myeloma cells. 217 79

Immunoglobulin G class human monoclonal antibodies to human cytomegalovirus (HCMV) were produced by the fusion of Epstein-Barr virus-transformed B cells and a murine myeloma cell line. The B cells were derived from the peripheral blood lymphocytes of healthy adult volunteers. Four hybridomas producing HCMV-specific monoclonal antibodies were established and each of four antibodies immunoprecipitated an HCMV-specific protein with a molecular weight of 68 kDa. However, the antibodies differed in some of their properties as characterized by indirect immunofluorescence assay and immunoblotting studies, due to the detection of different epitopes on the reacting antigen. None of the four antibodies had any virus neutralizing activity.
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PMID:Human monoclonal antibodies to human cytomegalovirus derived from peripheral blood lymphocytes of healthy adults. 217 39

To assess the frequency of IgE producing cells in humans a filter immunoplaque assay has been developed to detect IgE secretion from individual B lymphocytes in unfractionated peripheral blood mononuclear cells (PBMC). PBMC were incubated in microfilter plates containing nitrocellulose membranes coated with polyclonal anti-human IgE antibody, and the IgE production by a single cell was detected using a specific anti-human IgE monoclonal antibody followed by enzymatic development. The products of the enzymatic reaction were visualized as blue plaques on the membranes. The assay was both sensitive and specific as determined by: (1) a near 1:1 correlation between direct cell counts of an IgE producing myeloma cell line (U266) and the number of plaques in the filter immunoassay; and (2) the absence of detectable plaques generated by human B cells transformed by Epstein-Barr Virus (EBV) and producing only IgG or IgM. The presence of other cell types in PBMC did not affect the ability to detect IgE secreting cells. Replicate cultures of highly purified B lymphocytes, first transformed with EBV and then stimulated with recombinant human interleukin-4, produced IgE levels in culture supernatants that correlated closely with the number of IgE producing cells (r = 0.93; P less than 0.001). Furthermore, using the same transformed cells, the number of IgE secreting cells assessed by the immunoplaque assay was significantly correlated (r = 0.94; P = 0.002) with the number of IgE producing cells assessed by immunofluorescence staining of intracytoplasmic IgE. This assay provides a simple and direct method to assess the frequency of IgE producing lymphocytes in humans.
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PMID:Enumeration of IgE secreting B cells. A filter spot-ELISA. 220 65

Methods for forming multiple myeloma (MM) colonies are difficult because nonproliferative, but viable, plasma cells can survive for several weeks in culture and because MM cells tend to clump readily, forming pseudo-colonies. The present study describes a method for growing pure myeloma colonies in serum-free conditions in which genuine myeloma growth is unequivocally demonstrated. Growth was observed in 17 of 32 MM bone marrow samples. After a delay of 3-5 weeks, during which most cells died, Ig light-chain-restricted colonies emerged, expanded for approximately 3 weeks, and then showed no evidence of further proliferation. Cell doubling time was 8-10 days, and a significant number of cells in all cultures expressed Ki-67, having earlier lacked this nuclear proliferation antigen. In addition, colony formation was abrogated by irradiation, and two of eight cultures were successfully replated in 0.8% methylcellulose. Phenotypic analysis revealed a mixed population of plasma cells (RFD6+) and B-lymphocytes (CD19+, CAL-LA-), and cells were consistently Epstein-Barr virus negative. Culture of myeloma bone marrow by this serum-free method will allow appraisal of the role of various recombinant growth factors.
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PMID:A serum-free culture method for myeloma progenitors in vitro: proliferative and immunophenotypic characteristics. 240 57

Monoclonal antibodies against human prostatic acid phosphatase (PAPase) were produced by immunization of human primary spleen cell cultures. Dissociated spleen cells were cultured for 5-8 days in the presence of 100 ng/ml of PAPase and pokeweed mitogen (1:5000). Following immunization, B cells were isolated and infected with Epstein-Barr virus (EBV). Two weeks after EBV-transformation, cells were fused with either mouse myeloma cells (SP2/OAg14) or human/mouse heteromyeloma cells (SHM-D33). Hybrid clones were screened for anti-PAPase production. In 7 independent immunizations, the average fusion frequency was 3.6 per 10(6) lymphocytes. 18-32% of the hybridomas produced anti-PAPase; approximately 75% of these secreted IgM and 25% secreted IgG. Antibody specificity was determined by immunoassay and immunohistological studies. The procedures described here may be suitable for the production of human monoclonal antibody of a useful specificity.
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PMID:Production of monoclonal antibodies against prostatic acid phosphatase by in vitro immunization of human spleen cells. 241 32

Peripheral blood mononuclear cells (PBMC) from normal human donors were cultured in Marbrook flasks in the presence of purified IgG or IgA myeloma proteins. The culture supernatants were tested for their ability to suppress pokeweed mitogen (PWM)- or Epstein-Barr virus (EBV)-driven Ig synthesis by normal PBMC. Two supernatants from PBMC cultured with IgG and one from PBMC cultured with IgA were tested and suppressed PWM-driven Ig synthesis as measured by a reverse haemolytic plaque assay and by quantitation of the Ig secreted into the culture medium of the PWM-driven cells. This suppression was not restricted to the Ig isotype of the 'inducing' myeloma protein, but was extended to IgG, IgA, and IgM. The suppressive effect could be absorbed out with human IgG.
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PMID:Suppressor factors generated from human mononuclear cells by means of purified myeloma proteins. 241 68


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