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 influence of cell cycling on the density and binding properties of IgG2a Fc receptors and their associated antibody-dependent phagocytic activity was investigated with the P388D1 murine macrophage cell line. Unseparated macrophages and subpopulations of elutriated macrophages, enriched for cells in G1, S, and G2 + M phases were compared to detect possible differences in IgG2a-dependent phagocytosis. Suspensions of G2 + M phase cells were appreciably enhanced in phagocytic activity over G1-phase cells, which were less phagocytic than unseparated macrophage populations. An analysis of the binding of 125I-IgG2a myeloma protein disclosed that the IgG2a Fc receptor avidity remained essentially unchanged during cell cycle traverse, whereas the number of IgG2a Fc receptors more than doubled as cells cycled from G1 to G2 + M (1.5 X 10(5) vs 3.4 X 10(5) receptors per cell). With their increased size relative to G1 cells, and the resultant increase in receptor number, G2 phase cells should have more productive collisions with the antibody-coated target cells and greater phagocytic capacity.
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PMID:Macrophage cell cycling: influence on Fc receptors and antibody-dependent phagocytosis. 621

The relationship between the Fc region of trinitrophenylated (TNP)-immunoglobulins (Ig), and their ability to induce tolerance was examined. It was found that adult B cells responding to a T-independent (TI) antigen were tolerized by TNP11 human gamma globulin (HGG), but not by TNP10F(ab')2 fragments of HGG. Increasing the hapten density on the F(ab')2 fragments overcame their inability to induce tolerance. Thus, a TNP17-F(ab')2 was an effective tolerogen. Murine myeloma proteins of different IgG subclasses were similarly tested. A TNP12-IgG2a and a TNP11-IgG1 induced tolerance, whereas two TNP11-12-IgG3 did not. However, a more heavily haptenated TNP18-IgG3 was tolerogenic. These results suggest that lightly haptenated immunoglobulins depend upon Fc receptor binding to induce tolerance in adult B cells. Non-Fc receptor-binding carriers are not tolerogenic unless they are more heavily haptenated. Finally, T cell and macrophage depletion experiments suggest that the tolerogens act directly on the B cells.
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PMID:The use of haptenated immunoglobulins to induce B cell tolerance in vitro. The roles of hapten density and the Fc portion of the immunoglobulin carrier. 622 36

The reactivity of a soluble Fc receptor from a group C streptococcus ( FcRc ) was compared antigenically and functionally with the staphylococcal Fc receptor, protein A. Protein A and FcRc were found to inhibit each others' binding to the Fc region of human IgG, indicating that they bind to sites that are in close proximity on the Fc region of human IgG. The two bacterial Fc receptors were antigenically unrelated. Differences were observed in the species and subclass reactivity of the two receptors. The patterns of binding of protein A and FcRc under various conditions suggested that these receptors reacted with distinct regions on the Fc region of immunoglobulins. FcRc bound more efficiently to goat, sheep, and cow IgG, protein A bound more efficiently to dog IgG, and neither receptor bound to rat IgG. Differences were also observed in the reactivity towards human IgG subclasses. The FcRc bound to all samples of the four human IgG subclass standards. Protein A bound to IgG1, IgG2, and IgG4, and to one of two IgG3 myeloma proteins tested. The reactivity of our soluble FcRc corresponds to a type III streptococcal Fc receptor classified by the reactivity of intact bacteria.
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PMID:Streptococcal Fc receptors. II. Comparison of the reactivity of a receptor from a group C streptococcus with staphylococcal protein A. 623 68

We studied the effect of antibody on the growth of reovirus, serotypes 1 and 3, in P388D1, a continuous mouse macrophage-like cell line. Enhanced growth of virus was observed when cells were infected in the presence of nonneutralizing monoclonal antibodies or subneutralizing concentrations of either immune ascitic fluids or neutralizing monoclonal antibodies. Both enhancement of viral growth and neutralization were accompanied by an antibody-mediated increase in binding of radiolabeled virus to P388D1 cells. Although neutralization was seen only with monoclonal antibodies directed toward the sigma-1 surface protein of the virus, enhancement was observed with two monoclonal antibodies directed toward other surface proteins. Trypsin treatment of P388D1 cells abrogated enhanced growth of virus mediated by a mouse IgG2a antibody; preincubation with P388D1 with human IgG1 but not IgG2 myeloma proteins also abrogated enhancement by immune ascitic fluid or monoclonal antibody. These observations are compatible with known properties of P388D1 Fc receptors and support the role of the Fc receptor in antibody-mediated infection.
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PMID:Infection of a macrophage-like cell line, P388D1 with reovirus; effects of immune ascitic fluids and monoclonal antibodies on neutralization and on enhancement of viral growth. 630 93

Herpes simplex virus is known to induce an immunoglobulin-binding cell surface receptor in infected cells that utilizes a nonimmune mechanism. In the present paper, we report the immunoglobulin class and subclass specificity of this receptor. Of the human immunoglobulins G(IgG), IgA, IgM, and IgD, as well as the structurally related beta2 microglobulin, only IgG and its Fc portion exhibited an increased binding to herpes simplex virus-infected cells versus uninfected control cells. The IgG subclass specificity of the Fc receptor was studied in 37 radioiodinated IgG myeloma proteins representing all four subclasses. We found that IgG3 myeloma proteins did not bind to herpes simplex virus-infected cells to a greater extent than to uninfected cells. On the contrary, proteins belonging to the other subclasses exhibited an increased binding to herpes simplex virus-infected cells of the following relative magnitude: IgG4 greater than IgG1 greater than or equal to IgG2. This increment of binding could be abolished by addition of a large excess of human IgG Fc fragment. Evidence for the existence of a variable herpes simplex virus-specific binding ability between myeloma proteins belonging to the same IgG subclass was also obtained. Furthermore, we tested two other herpes simplex virus type 1 strains with a limited number of myeloma proteins with very similar results as with the herpes simplex virus type 1 F strain. Several sources of experimental artefacts were controlled, including the state of aggregation of the test proteins, the functional integrity of the Fc portion before and after radioiodination, and the subclass assignments. The implications for the biological role of the Fc receptor of herpes simplex virus are discussed.
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PMID:Human immunoglobulin class and subclass specificity of Fc receptors induced by herpes simplex virus type 1. 632 9

The percentage and absolute numbers of T lymphocytes bearing Fc receptor for IgG and IgM were evaluated in 13 patients with multiple myeloma and in a group of controls of the same age range. An increase in the percentage of the TG cells was found, whereas TM cell numbers were not different from those of the controls. In order to better define the properties of the TG lymphocytes, their ability to suppress the PWM-induced B cell differentiation was tested in an in vitro experimental assay. TG cells from multiple myeloma exert a suppressor activity as the TG of the controls in this system. The possible interpretation of suppressor T cell increases in these patients is discussed.
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PMID:Subpopulations of T-lymphocytes in multiple myeloma. 646 Oct 57

Thirteen IgG monoclonal antibodies to the envelope protein of 17D yellow fever virus (17D YF) were produced. All of the antibodies, whether type-specific to 17D YF or flavivirus cross-reactive, mediated antibody-dependent enhancement (ADE) of virus growth in P388D1 cells. There was no consistent relationship between ADE titres and the degree or pattern of neutralizing and/or haemagglutination inhibition activity. Monoclonal antibodies of different isotypes were used to investigate further the properties of P388D1 Fc receptors. The effects of trypsin treatment of P388D1 on ADE were similar to those previously described in experiments measuring direct binding of IgG proteins or rosetting of sheep red blood cells (SRBC) by macrophages, demonstrating sensitivity to digestion by trypsin of the Fc receptor for monomeric IgG2a but not for IgG2b. Aggregated myeloma proteins of IgG2a and IgG2b isotypes competed equally well with either IgG2a or IgG2b monoclonal antibodies to 17D YF in inhibition of ADE. However, selective inhibition by the homologous isotype was observed when rosetting by P388D1 of SRBC coated with IgG2a or IgG2b monoclonal antibodies was examined. These results may help to explain apparent discrepancies previously reported between experiments utilizing direct binding of IgG proteins and those using rosetting of antibody-coated SRBC to examine Fc receptor properties and indicate that immune complexes of virus and antibody resemble aggregated immunoglobulins with respect to macrophage Fc receptor function and differ from antibody-coated SRBCs.
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PMID:17D yellow fever virus infection of P388D1 cells mediated by monoclonal antibodies: properties of the macrophage Fc receptor. 685 70

Intact rabbit IgG antisheep erythrocyte antibodies, and the corresponding F(ab')2 fragments and partially reduced and alkylated IgG were studied for the capacity to induce cytotoxic plaque formation by normal human mononuclear leukocytes in surface monolayers of sheep erythrocytes. The F (ab')2 fragments did not induce plaque formation, whereas partially reduced and alkylated IgG antibodies had a good plaque-inducing capacity compared to untreated IgG anti-SRBC antibodies. The plaque formation was inhibited by human IgG, but not by IgM, IgA, IgD or IgE. Normal and myeloma IgG in aggregated form gave a stronger inhibition than the corresponding proteins. Strong inhibition was observed with IgG1, IgG3, and IgG4, and with IgG2 after aggregation. Both the Fc and pFc' corresponding to the C terminal domain gave a strong inhibition. Thus, the region of the IgG molecule involved in binding to the Fc receptor of the plaque-forming cells appears to be located within the CH3 domain. These observations, therefore, indicate that the plaque-forming cells are of monocytic origin.
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PMID:Specificity of receptors for IgG on human cytotoxic plaque-forming mononuclear leukocytes. Induction and inhibition of plaque-forming activity. 698 62

The specificity and kinetics of binding of purified monomeric human and murine myeloma immunoglobulins to Fc receptors were studied in a human promyelocytic cell line (HL-60). HL-60 cells contain approximately 20,000 Fc receptors per cell and bind human IgG1, IgG3 and mouse IgG2a with high affinity (dissociation constant of 5 to 10 nM). Kinetic studies of the binding of IgG1 to HL-60 cells demonstrate rapid exchange with ambient immunoglobulin with approximately one-half of the surface-bound IgG1 exchanging every 25 to 30 min at 37 degrees C. Estimation of the equilibrium binding constant from the rates of association and dissociation of IgG1 agrees well with the values obtained from Scatchard analysis of equilibrium binding of radioiodinated IgG1. Approximately one-half of the Fc receptors of HL-60 cells are capable of binding IgG1 complexed to Protein A. This result was independent of the concentration of Protein A (0.5 to 200 microM) or the time of incubation of IgG1 with Protein A. Studies in which Protein A was incubated with HL-60 cells at 37 degrees C then rapidly washed at 0 degrees C indicated that Protein A did not degrade Fc receptors or interact with the Fc receptor sites on HL-60 cells. The complexes formed between Protein A and IgG1 sedimented at 7 to 9S by ultracentrifugation. These results suggest that there are two types of Fc receptors on HL-60 cells, which can be distinguished by their ability to bind the IgG1-Protein A complex.
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PMID:Fc receptors of a human promyelocytic leukemic cell line: evidence for two types of receptors defined by binding of the staphylococcal protein A-IgG1 complex. 699 3

Since the U937 cell line expresses many characteristics of normal human monocytes and macrophages, we studied in detail its receptors for IgG by measuring direct binding and inhibition of binding of 16 radioiodinated human myeloma proteins representative of the 4 subclasses. As with normal monocytes, IgG1 and IgG3 bound most efficiently (17.3 and 15.7% bound), IgG4 less readily (7.1% bound), and IgG2 least readily (0.6% bound). Scatchard plots of IgG1 binding showed approximately 18,000 binding sites/cell with Ka approximately 10(8) liter/mol. IgG1 binding was inhibited equally well by IgG1 and IgG3 (50% inhibition with 0.26 +/- 0.03 and 0.26 +/- 0.09 microgram, respectively). IgG4 inhibited less readily (0.68 +/- 0.12 microgram). Three IgG2 proteins were not inhibitory (115 +/- 59) but one IgG2 myeloma inhibited well (0.89 +/- 0.47). IgG Fc fragments inhibited IgG1 binding 1000-fold more efficiently than Fab fragments, IgM, and IgA. Reciprocal inhibition experiments gave no indication of multiple receptor sites of differing specificities. In situ, the IgG1 receptor was resistant to proteases. The data suggest that the U937 Fc receptor may be a useful model of human macrophage structure and function.
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PMID:Characterization of the Fc receptor for IgG on a human macrophage cell line, U937. 700 Sep 5


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