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Biomedical subjects

H M Grey

Publications and source records attributed to H M Grey.

At least 19 recordsLinked to original sources
PubMed1979

Studies on the cytophilic properties of human beta2-microglobulin. II. The role of histocompatibility antigens.

The mechanism by which exogenously added beta2m binds to lymphoid cells has been explored. In the mouse it has been shown that beta2m remains associated with plasma membrane macromolecules following solubilization with NP-40 and that approximately 25-30% of the binding could be accounted for by binding to H-2 antigens. No binding to mouse immunoglobulin or Ia antigens could be detected. The sites for binding of the remainder of the cell-bound beta2m were not determined. Whereas normal human lymphocytes showed little or no capacity to bind exogenously added beta2m, it was found that phytohaemagglutinin (PHA)-stimulated cells could bind beta2m. This binding occurred optimally 2 days after PHA stimulation. Approximately half of the binding could be accounted for by binding to HLA antigens. The possible significance of these findings with respect to cellular interactions involving major histocompatibility complex gene products in the immune response is discussed.

Beta-Globulins↗
PubMed1979

Heterogeneity of binding of human IgA subclasses to protein A.

The ability of human IgA myeloma immunoglobulins to interact with protein A-containing Staphylococcus aureus was examined. Some IgA1 and IgA2 immunoglobulins bound to S. aureus although others of both subclasses failed to do so. These results were obtained by using both direct binding of radiolabeled immunoglobulins to S. aureus and with inhibition-type assays. Binding was dependent on the Fc fragment of IgA since there was no binding to S. aureus by an F(ab')2 fragment of IgA1. Nonprotein A-containing bacteria did not bind these immunoglobulins and isolated protein A interacted with radiolabeled immunoglobulins. This strongly suggested that protein A was responsible for the observed binding to S. aureus. These data indicate, in contrast to previous reports, that there is no simple relationship between IgA subclass and the capacity to bind to protein A.

Binding Sites, Antibody↗
PubMed1978

Physicochemical separation of two distinct Fc receptors on murine macrophage-like cell lines.

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.

Animals↗
PubMed1977

Receptors for IgG: subclass specificity of receptors on different mouse cell types and the definition of two distinct receptors on a macrophage cell line.

To evaluate subclass specificity and aggregate size requirements of IgG receptors on mouse cells, we measured binding of radiolabeled monomeric and BDB-aggregated mouse myeloma proteins fractionated into various sizes by means of gel filtration. Monomers, tetramers, and high molecular weight (approximately 10(7) daltons) aggregates were used. The various cells and cell lines studied could be segregated into three patterns of reactivity: (a) Macrophage and macrophage-like cell lines bound monomer IgG2a preferentially; high molecular weight IgG aggregates bound as follows: IgG1 = IgG2b = IgG2a. (b) Lymphoid lines D2N and S49 showed no capacity to bind monomer IgG2a; high molecular weight aggregates bound as follows: IgG1 = IgG2b less than IgG2a. (c) Other Thy-1-positive lymphoid cell lines (EL4 and L5178) and normal T and B cells showed no capacity to bind monomer IgG; high molecular weight IgG aggregates bound to a lesser extent than to cells of the first two categories in the following manner: IgG1 less than IgG2b greater than or equal to IgG2a. The variable pattern of reactivity of the macrophage-like cell lines with monomer and aggregated IgG suggested that two distinct receptors for IgG were present: one capable of binding IgG2a and another capable of binding all aggregates. Further evidence for this hypothesis was obtained by analysis of the inhibitory capacity of different IgG subclasses on the binding of aggregated IgG and monomer IgG2a to P388 cells. Inhibition of monomer IgG2a binding was effected only by monomer or aggregated IgG2a, whereas inhibition of binding of aggregated IgG1 or IgG2b was noted with aggregates of all three subclasses with some preferential inhibition by monomer IgG2b being observed. Furthermore, monomer IgG2b binding was preferentially inhibitable by monomer IgG2b. It is postulated from these data that two receptor sites are present on this macrophage-like cell line, one reactive with aggregates of all three subclasses as well as monomer IgG2b, and another receptor specific for monomer IgG2a which also binds aggregated IgG2a. Support of this concept was obtained by trypsinization experiments in which the binding of monomer IgG2a was markedly decreased by trypsin treatment of cells, whereas the binding of aggregated IgG2b was unaffected by this treatment.

B-Lymphocytes↗
PubMed1977

Mitogen activation of human chronic lymphatic leukemia cells. I. Synthesis and secretion of immunoglobulin.

The response of CLL (chronic lymphatic leukemia) lymphocytes to PHA, PWM, and Con A with respect to changes in surface markers and synthesis and secretion of immunoglobulin were examined. After PHA stimulation the percentage of cells bearing readily detectable surface immunoglobulin (SmIg) diminished rapidly whereas cells forming rosettes with sheep erythrocytes (E-rosettes) increased from less than 1% to 30 to 50%. The great majority of blast-transformed cells were E-rosette-positive cells with a small population of SmIg-positive blast cells also observed. Ig production in four of seven CLL lymphocyte populations was increased 2.5 to greater than 40-fold after 4 to 6 days of culture in the presence of PHA. In contrast, pokeweed mitogen did not affect Ig synthesis. Furthermore, the Ig secreted into the culture supernatant fluids from seven of eight CLL cases examined consisted almost entirely of free light chain molecules. In contrast, the cell lysates contained a significant proportion of intact Ig molecules. These results indicate that CLL cells can, under certain circumstances, be stimulated to synthesize and secrete increased amounts of Ig, but that there is a basic defect in the biosynthetic mechanism of these cells which result in the secretion of free light chains rather than intact immunoglobulin molecules.

B-Lymphocytes↗
PubMed1977

Solubilization and partial characterization of cell membrane Fc receptors.

We assayed detergent cell lysates and culture supernatant fluid of mouse cells for the presence of soluble FcR by means of a radioligand bioassay. Strict correlation was found between the amount of FcR present in soluble form and that found on intact cells. The soluble FcR of all cells tested, except mouse macrophages, behaved as lipoprotein by buoyant density centrifugation analysis and enzyme treatment. In the absence of detergent, soluble FcR sedimented as a 20S macromolecule; in detergent the material was 7 to 9S. It was readily bound by insolubilized IgG but not by insolubilized BSA or F(ab')2 fragments of IgG.

Animals↗
PubMed1976

PHA-induced activation of suppressor cells in normal human peripheral blood lymphocytes.

Normal human peripheral blood and tonsil lymphocytes can be stimulated to proliferate by phytohemagglutinin (PHA). When cells cultured with this mitogen for 3 days were transferred fo fresh autologous lymphocytes in fresh medium with PHA, the mitogen response of the fresh lymphocytes was suppressed. The suppression required the presence of viable cells, in that culture supernatants alone were not inhibitory and cell extracts showed only marginal inhibition. Approximately equivalent numbers of previously stimulated cells were required to produce optimal suppression of the PHA response of fresh cells. Cells irradiated after PHA stimulation were as effective as nonirradiated cells is causing suppression. PHA-stimulated cells also inhibited concanavalinA-induced proliferation and a mixed lymphocyte reaction. However, PHA-stimulated cells only partially inhibited the response to pokeweed mitogen. The suppressive effects were fully retained by a nylon-wool-enriched T-cell fraction but not by a B-cell-enriched fraction.

Cell-Free System↗
PubMed1976

Antigen heterogeneity of human B and T lymphocytes.

Rhesus monkeys were immunized with normal human lymphoid cells, cultured lymphoid cells, and chronic leukemic lymphocytes. Antisera were analyzed by cytotoxicity and immunofluorescence techniques to study the antigenic characteristics of human lymphocytes. In an attempt to obtain a reagent specifically reactive with T (thymus-derived) lymphocytes, an antispleen antiserum was absorbed with cellf from five B- (bone marrow-derived) cell lines. After absorption, the antiserum killed 60-75% of peripheral blood lymphocytes and 40-50% of tonsil cells, so that there was a relationship between the percentage of killed cells and the proportion of T lymphocytes. However, when cells after cytotoxic treatment were assayed for rosette formation with sheep erythrocytes (a T-cell marker) 5-20% of viable rosette-forming lymphocytes were found. Therefore, this antiserum was cytotoxic for only 75-90% of T cells. From studies performed with antisera prepared against spleen and B-cell lines, we conclude that lymphoblastoid cells are antigenically different and deficient in comparison to normal B lymphocytes. In addition, cultured B-cell lines appear to be antigenically heterogenous, as shown by the cytotoxic activity remaining in antispleen and anti-B-cell lines sera after absorption with various numbers and types of lymphoid cell lines. After absorption with normal lymphocytes, an antiserum produced against chronic lymphatic leukemia cells had specific activity associated with 12 chronic lymphatic leukemia cells tested. Absorption of the same antiserum with leukemic cells from two patients showed that a certain degree of antigenic heterogeneity also exists among chronic leukemic lymphocytes.

Agammaglobulinemia↗
PubMed1976

Some biological properties of beta2-microglobulin and its antibody.

beta2-Microglobulin on the surface of lymphocytes exists in two molecular forms, first as part of the HL-A antigen complex, and second as a free molecule unbound to other membrane macromolecules. Quantitative determinations of the numbers of molecules of beta2-microglobulin per lymphocyte when compared to published values for the numbers of HL-A molecules per cell are consistent with an excess of beta2-microglobulin compared to HL-A antigens on the cell surface. Turnover studies of beta2-microglobulin from the lymphocyte surface indicated that both beta2-microglobulin and HL-A components are metabolized at similar rates. beta2-Microglobulin appears to be released in the free form. HL-A antigens, if released from the cell surface, appear to be released unbound to beta2-microglobulin. The effects of anti-beta2-microglobulin antibody on lymphocyte activation, namely on the mixed lymphocyte reaction and on antigen induced proliferative response, were studied. Anti-beta2-microglobulin completely inhibited the mixed lymphocyte reaction and the antigen induced proliferative response.

Antibodies↗
PubMed1975

Beta2 microglobulin and lymphocytic infiltration in Sjögren's syndrome.

We measured salivary beta2 microglobulin concentrations in 49 patients evaluated for Sjögren's syndrome with a labial salivary-gland biopsy. The salivary concentration was elevated and a significant correlation (P less than 0.001) was found between the concentration and the degree of inflammation seen in the biopsy. Serum concentrations were increased in 135 patients with Sjögren's syndrome. Striking elevations were seen in patients with associated renal or lymphoproliferative complications. Three patients have an increase in serum beta2 microglobulin concentration in association with exacerbation of their disease, and six a decrease after clinically efficacious therapy. These data indicate that determination of beta2 microglobulin in saiva may provide a simple, noninvasive technic for estimation of the degree of local inflammation in autoimmune disease.

Adrenal Cortex Hormones↗
PubMed1975

Elevated salivary and synovial fluid beta2-microglobulin in Sjogren's syndrome and rheumatoid arthritis.

Beta2-Microglobulin is normally present in low concentrations in serum and other bodily fluids. By use of a radioimmunoassay, elevated concentrations of beta2--microglobulin were found in saliva and synovial fluid from patients with Sjogren's syndrome and rheumatoid arthritis, autoimmune inflammatory diseases that attack and destroy the salivary glands and articular tissues, respectively. Elevated beta2-microglobulin concentrations decreased in the saliva of two patients who simultaneously showed a clinical response to systemic treatment. Measurement of beta2-microglobulin in inflammatory fluids may offer a simple method of quantifying local activity in autoimmune states.

Arthritis, Rheumatoid↗
PubMed1975

Activation of T and B lymphocytes in vitro: presence of beta2-microblobulin determinants on allogeneic effect factor.

The biologically acitve entity termed allogeneic effect factor, which is produced by alloantigen-activated T cells and has been shown to regulate triggering and differentiation of B lymphocytes in vitro, has previously been demonstrated to possess antigenic determinants coded by genes in the I region of the H-2 gene complex of the mouse. The studies presented here provide evidence that allogeneic effect factor also possesses antigenic determinants identical or cross-reactive with beta2-microglobulin. These observations suggest an important role for beta2-microglobulin in the mechanism of cell-cell interactions and the consequences of such interactions on lymphocyte triggering and differentiation.

Animals↗
PubMed1975

Inhibition by anti-beta2-microglobulin antisera of responder cells and not of stimulator cells in the mixed lymphocyte reaction.

Specific antisera directed against beta2-microglobulin (B2m) have been shown to inhibit completely the mixed lymphocyte reaction (MLR). However, the mechanism of inhibition has been unclear. In the present study, further experiments were performed to determine the effect of anti-B2m on both the stimulator and responder cells in an MLR. The experimental design used was that of a xenogeneic MLR, using mouse and human lymphocytes. The ffect of anti-human B2m was studied in this system. Anti-human B2m inhibited the xenogeneic MLR only when human lymphocytes were used as responder cells and did not inhibit the MLR when they were used as stimulator cells...

Animals↗
PubMed1975

Studies on the cytophilic properties of human beta2 microglobulin.

Human beta2 microglobulin is cytophilic for mouse, rat, and to a lesser extent guinea pig lymphocytes and polymorphonuclear leukocytes but not for human, rabbit, chicken, frog, and turtle cells, nor for any mature erythrocytes tested. Mouse splenic lymphocytes bind 5- 7-fold more beta2 microblobulin than thymocytes although hydrocortisone-resistant thymocytes resemble spleen cells in this regard. The beta2 microglobulin binding by B and T cells in mouse spleen is similar. The structure responsible for beta2 microglobulin binding to the surface of cells is distinct from the Fc receptor specific for aggregated IgG.

Animals↗