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Biomedical subjects

M W Fanger

Publications and source records attributed to M W Fanger.

At least 109 records · Page 6Linked to original sources
PubMed1982

Monoclonal antibodies reactive with human myeloid leukaemia cells.

Hybridomas producing monoclonal antibodies that bind to determinants on myelogenous leukaemia blast cells were developed using fresh leukaemia blasts as immunogens. These monoclonal antibodies were used to quantitate the amount of a variety of antigens on both leukaemia and normal blood cells in a radioimmunoassay. The ability of these antibodies to mediate complement-dependent lysis of leukaemia cells and normal blood cells was evaluated. Significant quantitative differences in the expression of a variety of cell surface antigens were observed among different myeloid leukaemia cell samples, normal cells, and other forms of leukaemia. However, none of the monoclonal antibodies studied were found to be specific for myeloblasts. Despite the fact that these antibodies bound to both leukaemia and normal cells, several of them mediated complement-dependent cytotoxicity which was restricted to leukaemic myeloblasts (AML-1-211, AML-2-30, CML-18, CML-75, CML-115, and CML-150). None of these clones, alone or in any combination, were capable of lysing normal lymphocytes or monocytes. Others were specifically cytotoxic to leukaemia cell lines (AML-1-99), B cells and some leukaemia samples (AML-2-9), and myelomonocytic leukaemia cell samples and normal monocytes (AML-2-23). Several of the monoclonal antibodies from this panel appear to be promising for future clinical applications.

Antibodies, Monoclonal↗
PubMed1982

Receptors for IgA on rabbit lymphocytes. II. Characterization of their binding parameters for IgA.

The specificity of rabbit receptors for IgA (RFc alpha) was investigated on lymphocytes isolated from the Peyer's patches and spleen. Specifically was determined by the inhibition of IgA rosette formation with intact and proteolytic fragments of rabbit and human secretory IgA (SIgA), human myeloma proteins, and secretory component. RFc alpha bound human SIgA as efficiently as rabbit SIgA. Of the human IgA tested, RFc alpha preferentially bound to the IgA2 subclass and most avidity to a multimeric IgA molecule. In addition., the site of the RFc alpha-IgA interactions was localized to the C alpha 2 domain in the Fc portion of IgA. RFc alpha on spleen lymphocytes showed the same pattern of binding specificity toward the human IgA subclasses as the RFc alpha on lymphocytes from Peyer's patches. However, differences between the spleen and Peyer's patches were observed in the interaction of RFc alpha and the rabbit IgA subclasses. RFc alpha on lymphocytes from the Peyer's patches bound the rabbit IgA-g subclass more efficiently than the rabbit IgA-f subclass, whereas the converse was true for the spleen RFc alpha. Human secretory component inhibited IgA but not IgG or IgM rosette formation as a result of its interaction with lymphocytes. These studies suggest: 1) that there may be two types of RFc alpha expressed by lymphocytes in certain tissues, and 2) that there are two closely associated receptors on the lymphocyte--one specific for secretory component and the other for structures within the C alpha 2 domain of IgA.

Animals↗
PubMed1981

Expression of receptors for IgA in hairy-cell and other B-cell leukaemias.

In six cases of both hairy-cell leukaemia (HCL) and chronic lymphocytic leukaemia (CLL) it was shown that the pathological cells express receptors for the Fc portion of IgA (RFc alpha). Many of the cells simultaneously expressed receptors for IgA, IgM and IgG, and blocking studies showed that these are distinct receptors. In contrast, the malignant cell of most of the various other B-cell leukaemias studied showed low levels of RFc alpha expression. The significance of the results is briefly discussed and it is suggested that receptor expression may be a marker of certain stages of B-cell development.

B-Lymphocytes↗
PubMed1981

Synergy between IgG and monoclonal IgM antibodies in antibody-dependent cell cytotoxicity.

Hybridoma-derived mouse monoclonal IgM anti-ox erythrocyte (ORBC) antibodies, which differed in their ability to exhibit complement-mediated cytotoxicity, direct agglutination and sensitization of indicator cells for detection of receptors for IgM on erythrocytes, failed to mediate antibody-dependent cell cytotoxicity (ADCC) by human K cells. Polyclonal rabbit IgM anti-ORBC antibodies were also incapable of mediating ADCC. However, one of the IgM monoclonal antibodies studied (clone 100) was highly efficient in synergizing with IgG in ADCC, especially when the E rosette-forming enriched fraction was used as a source of effector cells. This synergy was greater after overnight incubation of the lymphocytes and was partially blocked by human IgM. Since all the monoclonal antibodies studied bound efficiently to target ORBC as determined by the additional binding of 125I-labeled anti-k antibodies, the synergy did not appear to be due to a quantitative difference in the binding capacity of the antibodies. That the synergistic effect of purified clone 100 IgM was not due to heterophile IgG antibody was indicated by its sensitivity to reduction and lack of binding to a protein A column. The data are discussed in terms of the possible in vivo relevance of IgG-IgM synergy to immune protection, especially during the development of a primary antibody response when limiting amounts of specific IgG antibodies could be made more effective with the more abundant IgM antibodies.

Animals↗
PubMed1981

Receptors for IgA on human lymphocytes. II. Organ distribution and relationships with other Fc receptor-bearing populations.

Lymphocyte populations expressing receptors for IgA (RFc alpha) in several human lymphoid tissues were numerically evaluated using a highly sensitive and specific indicator system. The percentages of RFc alpha-bearing lymphocytes were, in thymus, 9%; bone marrow, 14%; tonsil, 38%; cord blood, 34%; and adult blood, 55%. In adult and cord blood, RFc alpha were primarily associated with the T-lymphocyte populations as defined by their ability to bind sheep erythrocytes (SE). A large percentage of the peripheral T-lymphocyte population expressed both RFc alpha and receptors for IgM (RFcmu), whereas few T lymphocytes expressing receptors for IgG also displayed RFc alpha. Although a small number of peripheral non-T cells also expressed RFc alpha, they appeared to have fewer or less avid receptors than the RFc alpha-bearing T lymphocyte population. Both bone marrow and tonsil lymphocytes of both T and non-T populations expressed RFc alpha. Furthermore, the RFc alpha-bearing non-T population in both tonsil and bone marrow was quite large, 39 and 26%, respectively. These studies document the ubiquity of RFc alpha and its expression on the same peripheral lymphocyte population as RFcmu and indicate that RFc alpha is associated with several functionally different lymphocyte subpopulations including those involved in regulation (help) and antibody-dependent cell cytotoxicity.

Adolescent↗
PubMed1980

Subpopulations of human peripheral granulocyes and monocytes express receptors for IgA.

Receptors for the Fc portion of immunoglobin on human peripheral blood cells were enumerated by rosette formation with ox erythrocytes sensitized with rabbit IgG, IgA, and IgM. A large percentage of purified polymorphonuclear leukocytes and monocytes were found to express receptors for IgA. These receptors were also found to exist on a significantly greater percentage of lymphocytes than was previously observed. The receptors for IgA were specific, as verified by blocking studies using purified human immunogloblins. In addition, some polymorphonuclear leukocytes and monocytes were observed concomitantly to posses independent receptors for both IgG and IgA. These studies may indicate that IgA can cooperate with monocytes or polymorphonuclear leukocytes through receptors for IgA on these cells and perhaps mediate immune defense on mucosal surfaces. Initial studies on antibody-dependent cellular cytotoxicity suggested that IgA alone is ineffectual in supporting cytolysis by nonactivated human peripheral blood cells.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1980

Receptors for IgA on rabbit lymphocytes. I. Distribution, specificity, and modulation.

The distribution of IgA binding lymphoid cells in the rabbit was determined by using ox erythrocytes coated with specific secretory IgA. After overnight incubation at 37 degrees C, the average percentage of IgA binding lymphocytes detected in major IgA-producing organs (Peyer's patches, 14.4%; appendix, 8.4%; and mesenteric lymph nodes, 11.3%), was generally higher than that detected in systemic lymphoid tissue. Lymphocytes bearing receptors for IgA (RFc alpha) were detected immediately after isolation only in the spleen and failed to appear after overnight incubation only in the thymus. That these receptors were distinct from receptors for IgM or IgG was demonstrated by cross-blocking studies with purified IgG, IgM, and IgA immunoglobulins. RFc alpha were sensitive to pronase digestion at 1 mg/ml and were regenerated with overnight incubation. In preliminary studies designed to evaluate modulation of this receptor, it was found that a significant increase in the percentage of cells expressing RFc alpha could be induced by antibodies specific for rabbit immunoglobulin. This information as a whole is consistent with the premise that RFc alpha-expressing lymphocytes may be involved in the regulation or expression of IgA-mediated immunity.

Animals↗
PubMed1979

Receptors for IgM on human lymphocytes. I. Detection of receptors on freshly drawn lymphocytes and at physiological temperature.

Receptors for the Fc portion of IgM (RFcmu) have previously been found to be primarily associated with the T lymphocyte subpopulation in humans, and their detection has frequently required overnight incubation of the cells before assay. In the present study, using highly sensitized indicator cells (EAmu), lymphocytes with receptor for IgM (EAmu-RFC) were detected immediately after isolation from human peripheral blood. Identification of EAmu-RFC on freshly isolated lymphocytes was greatly facilitated by assay at room temperature (RT) or 37 degrees C, implying that analogous interactions between IgM-antigen complexes and lymphocytes with receptor for IgM normally occur in vivo. These results seem to indicate that some RFcmu on lymphocytes may be occupied by IgM and/or IgM-antigen complexes in vivo and that immediately after isolation many RFcmu are still occupied and unavailable for interaction with EAmu. It is suggested that the successful competition of IgM-antigen complexes for RFcmu on T lymphocytes is the signal for and/or mechanism of expression of help by the lymphocyte. The sensitivity of the assay for EAmu-RFC also permitted the identification of a small subpopulation of RFcmu+ lymphocytes in the non-T cell fraction of the peripheral blood of some individuals.

Antibody Affinity↗
PubMed1979

Receptors for IgM on human lymphocytes. II. Mitogen-induced modulation of receptor expression.

Human peripheral lymphocytes undergoing blastogenesis induced by phytohaemagglutinin (PHA) or concanavalin A did not express receptors for the Fc portion of IgM (RFcmu). Furthermore, treatment of lymphocytes with PHA produced a dose-dependent loss of RFcmu which began as early as 5 hr after exposure to the mitogen. Within 24 hr after the addition of PHA, the percentage of lymphocytes expressing RFcmu had decreased from 65% to 4%. Under the same conditions of treatment, the expression of the receptor for sheep erythrocytes (E) was unchanged. These findings seemed inconsistent with a direct blocking effect of PHA but suggested that PHA induced a time-dependent modulation (switch off) of expression of RFcmu. Pronase cleavage of surface proteins on cells incubated with PHA for 24 hr followed by overnight incubation showed an almost complete irreversibility of RFcmu modulation up to 72 hr later. Studies using T cells isolated by E-rosetting showed that RFcmu modulation predominantly occurred on T cells. The modulation of RFcmu expression is discussed in terms of its possible role in the immune response.

Humans↗
PubMed1979

Receptors for IgM on human lymphocytes. III. Specificity of receptors.

Receptors for the Fc portion of IgM (RFcmu) can be detected on a large percentage of human peripheral lymphocytes. To approach an understanding of the function of these receptors we have examined the relative efficiencies of different preparations of human IgM and their F(c)5 mu fragments in binding to RFcmu. This was measured by blocking rosette formation between lymphocytes and IgM-sensitized ox erythrocytes (EAmu). IgM from pooled normal human serum completed blocked formation of IgM rosettes (EAmu-RFC) at much lower concentrations than IgM preparations from individual Waldenström's macroglobulinaemic patients (WM). The differences in effectiveness of these IgM preparations in inhibiting EAmu-RFC suggested the existence of receptors for subclasses of IgM on different subpopulations of human lymphocytes. F(c)5 mu fragments of IgM were more effective in blocking EAmu-RFC than the parent molecule, which was in turn more efficient than the 8S subunit. These results indicate that F(c)5 mu may have more Fc regions exposed per molecule for binding to the matrix of RFcmu than pentameric IgM and that Fc multivalency may be important for the stable binding of IgM to RFcmu.

Adult↗
PubMed1977

Plasma cell leukemia with excretion of half-molecules of immunoglobulin A (alpha1 lambda1).

A patient with plasma cell leukemia and myelofibrosis excreted free immunoglobulin light chains and an abnormal monoclonal immunoglobulin (Ig) A in her urine. The IgA that was present in serum and urine had a sedimentation coefficient of 4.0 S. The molecule was comprised of both heavy and light chains but was antigenically deficient compared to normal IgA. As excreted in the urine, the protein appeared to be a half-molecule of IgA, with a partial deletion in the heavy chain, probably involving part or all of the C-terminal domain.

Female↗