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)

To investigate the antigenic relationship between the macrophage and lymphocyte Fc receptors (FcR), a monoclonal antibody capable of blocking mouse macrophage Fc receptors was selected. Hybrids were formed by fusing the P3U1 mouse myeloma and spleen cells from a rat immunized with the mouse macrophage-like cell lines J774 and P388D1. The Fab fragment of the monoclonal IgG secreted by clone 2.4G2, inhibited the trypsin-resistant Fc receptor II (FcRII), which is specific for immune aggregates of mouse IgG1 and IgG2b, but had no inhibitory effect on the trypsin-sensitive Fc receptor I (FcRI), which binds monomeric IgG2a and erythrocytes coated with IgG2a. Thus, the monoclonal 2.4G2 IgG appeared to be specific for macrophage FcRII. Further evidence that the 2.4G2 IgG was directed against FcRII came from binding studies of the monoclonal antibody to J774 cells and a series of independently isolated variants which do not express FcRII. These variants of J774 bound 5% as much of the monoclonal antibody as the parent line, which bound 600,000 molecules of 2.4G2 IgG per cell. The antigenic relatedness of mouse lymphocyte FcR to mouse macrophage FcRII was demonstrated by the binding of 2.4G2 IgG to FcR-bearing lymphoid cell lines and the inhibition of the lymphocyte FcR by the monoclonal antibody. Preincubation of spleen cells and peritioneal cells with 2.3G2 IgG likewise inhibited rosette formation with ox erythrocytes coated with rabbit IgG. The ability of the hybridoma IgG to inhibit mouse FcRII was independent of the major histocompatibility complex. The 2.4G2 IgG antigenic determinant was not present on rat, guinea pig, rabbit, or human FcR-bearing cells.
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PMID:Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors. 9 Jan 8

Seventy-four patients with multiple myeloma, 17 untreated and 57 treated, were studied to characterize their peripheral blood lymphocytes. PBL were studied for E, EAC, and EA rosette-forming cells, SIg, and Fc receptor-bearing cells. The responses to HA, Con A, and PWM were assessed as well as their ability to stimulate or to respond in a MLC. Finally, the capacity of mitogen-stimulated lymphocytes to lyse Chang cells, CRBC, and PHA-stimulated lymphoblasts was examined. These results were compared with a group of normals and patients with benign monoclonal gammopathy. In untreated myeloma patients there was a normal percentage of T cells, but an abnormal distribution of B cells as judged by a decrease in SIg-bearing cells, as well as an increase in EAC rosette-forming cells. Subpopulation analysis showed a marked increase in EAC rosette-forming cells without SIg. PHA, Con A, and PWM, and response in MLC were all normal. However, the ability to stimulate in MLC was significantly depressed. Treated myeloma patients had similar findings, except that the response to PWM was significantly depressed. The capacity of PWM-stimulated cells to lyse target cells was depressed in both groups. The results indicate that, in the peripheral blood of myeloma patients, there are populations of lymphocytes characterized by the presence of the EAC receptor without SIg, which are deficient in the capacity to stimulate an MLC response and the ability to be cytotoxic when stimulated by PWM. The results form a baseline for the study of abnormal lymphoid function in human myeloma.
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PMID:Multiple myeloma: an immunologic profile. I. Peripheral blood studies. 14 Jan 96

Mouse splenic macrophages were fused with cells of the mouse myeloma line P3-X63-Ag8 in the presence of inactivated Sendai virus. Two continuously growing hybrid cell lines were established from fusion mixtures. These hybrid cell lines exhibited macrophage-like morphology and continued to express macrophage derived Fc receptor activity even after prolonged culture in vitro.
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PMID:Maintenance of Fc receptors in hybrid cell lines obtained by fusing mouse splenic macrophages with mouse myeloma cells. 22 69

Three mouse immunoglobulins with altered heavy chains have been used to study the specificity of the mouse IgG2b Fc receptor on mouse macrophages. These immunoglobulins were synthesized by variant clones derived from the MPC 11, IgG2b-producing mouse myeloma cell line. One variant, whose Fc receptor. A second variant, which makes a short heavy chain lacking the CH3 domain, binds specifically to the IgG2b Fc receptor. The third variant makes a hybrid IgG2b-IgG2a heavy chain whose CH3 domain is enterely IgG2a-like and binds to both IgG2a and IgG2b Fc receptors. These data suggest that the binding of mouse IgG2b immunoglobulins to the mouse macrophage Fc receptor involves a site within the CH2 domain and indicate that immunoglobulins with altered heavy chains are a useful tool to probe Fc receptors.
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PMID:Site of binding of mouse IgG2b to the Fc receptor on mouse macrophages. 47 65

By using radiolabeled myeloma proteins specific for each of two distinct Fc receptor activities on macrophage-like murine cell lines ("aggregated IgG FcR" activity and "monomer IgG2a FcR" activity), we have been able to detect solubilized FcR of both types in detergent lysates of these cells. The two solubilized Fc receptors can be distinguished and physically separated from one another by means of affinity chromatography and by sucrose gradient centrifugation. They also differ in their sensitivity to phospholipase C. The detergent solubilized monomer IgG2a FcR can be removed from solution with a Sepharose IgG2a column, has an S value of 4 to 5 and is resistant to phospholipase C. The solubilized aggregated IgG FcR does not bind to insolubilized IgG2a, has an S value of greater than 19, and is sensitive to phospholipase C treatment. We conclude from these studies that two different cell membrane macromolecules are responsible for the Fc receptor activities observed in macrophage-like cell lines.
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PMID:Physicochemical separation of two distinct Fc receptors on murine macrophage-like cell lines. 68 52

Anti-idiotypic antibody raised against the BALB/c myeloma proteins TEPC-15 or HOPC-8 inhibits induction of the immune response to phosphorylcholine (PC). (Fab')2 and Fab' fragments from anti-idiotype serum were prepared and anti-idiotypic antibody was purified by absorption and elution from idiotype or anti-IgG subclass immunoabsorbents. The parent material, the purified anti-idiotypic antibodies and the Fab' fragments were assayed for: i) binding to the idiotype by using a sensitive radioimmunoassay, and ii) specific suppression of the response to PC in vitro. The correlation of binding to suppression was very similar for anti-idiotype serum and both kinds of purified antibody. However, the Fab' fragments only bound to the idiotype and did not suppress. These findings indicate that the Fc portion of anti-idiotypic anti-receptor antibody (ARA) is essential for inducing suppression but that ARA-induced suppression is independent of the IgG isotype. It is postulated that idiotype suppression is mediated by the interaction of anti-idiotype with the antigen receptor and the Fc receptor thereby cross-linking both receptors.
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PMID:Immune response to phosphorylcholine. III. Requirement of the Fc portion and equal effectiveness of IgG subclasses in anti-receptor antibody-induced suppression. 91 88

The expression of membrane immunoglobulin (mIg) was examined in three cloned MPC11-derived mouse myeloma cell lines. Membrane immunofluorescence studies demonstrated that IgG2b producer cells (P1) had complete IgG molecules, L-chain producer (L1) had only L-chain determinants and nonproducer (NP2) did not have any Ig determinants on the cell surface. An Ig receptor, with characteristics different from B lymphocyte Fc receptor, has been found to be present on secreting cells (P1 or L1), but not on the NP2 cell variant. The data reported in the present paper indicate that the expression of mIg and of the Ig receptor molecule is clearly correlated with the process of secretion. In the light of previous data reported on Ig secretion, a model is proposed which correlates the process of secretion with the expression not only of mIg, but also of the receptor for Ig.
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PMID:Membrane Ig on MPC11 myeloma cells: correlation between the expression of membrane Ig, a receptor for Ig and the process of secretion. 97 17

A wide range of cell populations were examined for Fc receptor (FcR)-bearing T cells: thymus, spleen, peritoneal cells, and T cells activated to H-2 antigens in spleen (ATC spleen) and in thoracic duct lymph (T-TDL). In addition, B lymphocytes from thoracic duct lymph of athymic nude mice and a Thy-1-positive, FcR-positive thymoma served as control cell populations. Reagents used were aggregates of human gamma-globulin and of various mouse myeloma proteins (IgG1, IgG2a, IgG2b), radioiodinated antigen-antibody complexes, and sheep erythrocyte antibody rosettes. Labeling techniques involving radioautography and immunofluorescence were used to demonstrate FcR by one of the above reagents and to identify T cells either by staining with anti-Thy-1.2 or by a specific rabbit anti-mouse T cell serum, or by failure to stain with anti-mouse immunoglobulin. In some experiments phagocytic cells were removed whereas in others they were identified by their capacity to engulf latex particles. Approximately 25% of cells with T cell markers were FcR-bearing cells in thymus, normal spleen, and peritoneal cavity, and 17% in ATC spleen. FcR on T cells in peripheral lymphoid tissues were detectable by aggregates of HGG and myeloma proteins and by radioiodinated immune complexes. Those on T cells in thymus were revealed only by aggregates of HGG. Circulating T cells (T.TDL) failed to display FcR: a) despite the use of a wide range of the above labeling techniques, each of which was shown to detect FcR on other T cells, thymoma cells, and B cells, and b) even after removal of Ig associated with their cell membranes. In contrast to B cell FcR which bound IgG1 preferentially, those on T cells bound both IgG1 and IgG2, raising the possibility that the FcR on T cell is distinct from that on B cell. It is concluded that FcR-bearing T cells represent a subpopulation of cells within the thymus and the secondary lymphoid tissues.
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PMID:A subpopulation of T cells bearing Fc receptors. 110 Jul 23

A human anti-dextran serum, EAK, with IgG antibodies restricted to subclass IgG2, was tested for its capacity to induce lysis of dextran-coated chicken erythrocytes by normal human lymphocytes or monocytes. Another human anti-dextran serum, RGM, with most antibodies belonging to sublass IgG1, and a hyperimmune rabbit anti-dextran serum were used for reference. In lymphocyte-mediated erythrolysis, serum EAK gave rise to 51-Cr release varying from 20% to 80% in different experiments. The hyperimmune rabbit serum was 100 to 1000 times more active, whereas serum RGM was consistently negative. These results correlated well with the concentration of anti-dextran antibodies in these sera. In monocyte-mediated erythrolysis serum EAK had a somewhat higher titer than in lymphocyte-mediated lysis, and serum RGM had a weak but significant activity at low dilutions. Serum EAK also induced erythrophagocytosis by monocytes. Ultracentrifugation did not significantly decrease the inductive capacity of this serum. The results show that antibodies of human sublass IgG2 are efficient inducers of effector functions in both lymphocytic and monocytic cells. Myeloma proteins of the four IgG subclasses were tested for inhibitory capacity in lymphocyte- or monocyte-mediated erythrolysis. Either serum EAK or the rabbit reference serum was used for induction of erythrolysis. Individual myeloma proteins within and between the subclasses varied considerably in inhibitory power. However, whereas IgG1, IgG2, and IgG3 proteins inhibited lymphocyte-mediated erythrolysis induced by either type of antiserum, the two IgG4 proteins tested were essentially negative. These results suggest a lack of specificity of the Fc receptor for subclasses IgG1, IgG2, and IgG3 in both heterologous and homologous inhibition. In monocyte-mediated erythrolysis, IgG1 and IgG3 were strong inhibitors, whereas inhibition by IgG2 and IgG4 was weak and inconsistent. This pattern was seen regardless of whether and inducing antiserum was of rabbit or human origin. Similar results were obtained in monocyte-induced erythrophagocytosis induced by serum EAK. These and previous results suggest that effector cells of the lymphocytic (K cell) variety have Fc receptors different from those of monocytic cells. However, the basis for the differences observed in the inhibition tests remains to be elucidated.
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PMID:Destruction of dextran-coated target cells by normal human lymphocytes and monocytes. Induction by a human anti-dextran serum with IgG antibodies restricted to the IgG2 subclass. 117 21

A system of exon "modules" was produced from the functionally rearranged epsilon-heavy gene isolated from the rat IgE-secreting immunocytoma IR162. The five individual exons, encoding the variable and constant region domains, were isolated and subcloned into the multiple cloning site of a pair of plasmid vectors with opposed orientation multiple cloning sites. The use of opposed orientation multiple cloning sites and the flanking restriction enzyme sites contained therein allows for the modular manipulation of the gene. These exon modules were initially used to reconstruct the epsilon-heavy chain gene into the native configuration to demonstrate the efficacy of the modular system for synthesis of IgE. Upon transfection into the rat myeloma cell line Y3, the reconstructed gene produced a polypeptide that associated with the endogenous light chain polypeptide and was secreted from the cell as tetrameric IgE. All physical and functional characterizations indicate that the IgE molecule produced is indistinguishable from native IR162 IgE. This modular system of exons will facilitate the manipulation of IgE structure through the systematic assembly of different epsilon-heavy chain mutant constructions. The resulting novel IgE proteins will be very useful to study the molecular nature of the interaction of IgE with its Fc receptor.
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PMID:The expression and characterization of rat IgE produced by construction of the epsilon-heavy chain gene from exon modules. 153 68


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