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Biomedical subjects

H B Dickler

Publications and source records attributed to H B Dickler.

At least 55 records · Page 3Linked to original sources
PubMed1977

Differences between the Fc receptors of two lymphocyte subpopulations of human peripheral blood.

The Fc receptors of human peripheral blood lymphocytes bearing stable membrane Ig (B cells) and those bearing cytophilic membrane Ig (UL cells) were evaluated for binding avidity and interaction with human 'Ia-like' alloantigens. Titration experiments showed that binding of soluble antigen-antibody complexes to UL cells was readily detected at low concentations (5-10 microgram/ml), whereas high concentrations (400-800 microgram/ml) were necessary to detect binding to most B lymphocytes. Binding at all concentrations was dependent on an intact Fc portion of the antibody molecule within the antigen-antibody complex. F(ab')2 fragments of antibodies against human 'Ia-like' antigens inhibited binding of complexed Ig to B cells but not UL cells. These differences are compatible with the possibility that the Fc receptors of the two cell populations are distinct molecular entities or, alternatively, are the same molecules and differ in quantity, distribution, or mobility on the surface of the two cell types.

Antigen-Antibody Complex↗
PubMed1977

Antibody-dependent cellular cytotoxicity effector cells lack Ia antigens.

Surface immunoglobulin (sIg)-positive and sIg-negative subpopulations of macrophage-depleted murine splenic lymphocytes were obtained by Sephadex anti-Fab immunoabsorbent fractionation. These lymphocyte subpopulations were analyzed for the presence of Thy 1 and Ia alloantigens and also for Fc receptors by fluorescence microscopy. Concurrently, these lymphocyte subpopulations were studied for effector cell activity in antibody-dependent cellular cytotoxicity (ADCC). Effector cells mediating ADCC were contained in the sIg-negative lymphocyte subpopulation and sIg-positive lymphocytes did not mediate cytotoxicity. The majority of sIg-positive lymphocytes were found to bear Ia antigens and Fc receptors, and these cell surface structures were associated in that treatment of these cells with anti-Ia sera inhibited binding of complexed immunoglobulin to Fc receptors. In contrast, most sIg-negative, Thy 1-negative lymphocytes lacked Ia Antigens, and the Fc receptors detected on such cells were not blocked by anti-Ia sera. In addition, a small subpopulation of sIg-negative, Ia antigen-positive, Fc receptor-positive lymphocytes was found. Elimination of this subpopulation of Ia antigen-positive cells from sIg-negative lymphocytes, by treatment with anti-Ia serum and complement, did not diminish ADCC effector cell activity in the resultant cell population when compared with untreated sIg-negative lymphocytes. Thus, in murine spleen, nonphagocytic mononuclear cells that lack both sIg and Ia antigens were shown to mediate ADCC.

Animals↗
PubMed1976

Association between Ia antigens and the Fc receptors of certain T lymphocytes.

The Fc receptors of thymic and splenic T lymphocytes were detected using indirect immunofluorescence and soluble antigen-antibody complexes. 10-20% of thymocytes and 40-50% of Thy-1-positive splenic lymphocytes bound antigen-complexed Ig. The binding to thymocytes was partially inhibited (45-74%) by antibodies against antigens determined by the I region of the H-2 complex, but not by antibodies against K- or D-region antigens or Thy-1 antigen. The inhibition did not require the Fc portion of the inhibiting antibody. These results provide evidence that Ia antigens and the Fc receptors of some T lymphocytes are associated, and that the populations of T cells which bear these moieties at least partially overlap.

Animals↗
PubMed1976

Studies of Ia antigens on murine peritoneal macrophages.

Murine peritoneal cells, both induced and noninduced, were examined for Ia antigens by a variety of techniques. Complement-mediated cytotoxicity and indirect immunofluorescence, analyzed by both visual microscopy and the fluorescence-activated cell sorter, detected Ia antigens on the surface of an average of 8% to 15% of cells with the morphologic and functional characteristics of macrophages. Internal radioisotope labeling studies showed that these antigens were actually synthesized by the macrophages. The antigens were borne on molecules which consisted of two coponents with apparent molecular weights of roughly 33,000 and 25,000 daltons. At least some of these molecules existed as a two-chain structure of 58,000 daltons linked by disulfide bonds. Although macrophage Ia antigens appeared to be structurally similar to the Ia antigens found on spleen cells, the radioisotope labeling studies indicated that the quantity of labeled Ia-bearing molecules isolated from peritoneal macrophages was at most 1/15 that found for B lymphocytes. In addition, anti-Ia antisera failed to inhibit the binding of heat-aggregated immunoglobulin to the Fc receptor of macrophage populations, similar to the low levels of Ia antigens found in T-lymphocyte populations. These studies suggest that Ia antigens exist only a subpopulation of peritoneal macrophages. Alternatively, all cells in the population might bear small amounts of Ia antigens with only a fraction having sufficient numbers of molecules to be detected by the assay systems used.

Animals↗
PubMed1976

Lymphocyte binding of aggregated immunoglobulin.

This paper describes lymphocyte binding of aggregated immunoglobulin, which appears to bind to B lymphocytes and the third lymphocyte-like cell population. The applications of aggregated Ig binding are also discussed, and the relation to Fc receptors and Ia-like antigens.

B-Lymphocytes↗
PubMed1975

Inhibition of lymphocyte mitogenesis by immobilized antigen-antibody complexes.

Mouse spleen cells, cultured on surfaces coated with antigen-antibody complexes, are inhibited from responding to the B-cell mitogens, lipopolysaccharide, lipid A, Pneumococcal polysaccharide SIII, and poly I:C. The response to the T-cell mitogen, concanavalin A, is also substantially inhibited by immobilized antigen-antibody complexes, but specific inhibition of the response to phytohemagglutinin is minimal. Control experiments showed that immobilized complexes prepared from IgG F(ab')2 fragments and IgA antibodies (both of which fail to bind to Fc receptors when complexed to antigen) did not show significant inhibitory activity when compared with the inhibition observed with complexes prepared from whole IgG. Suspensions of antigen-antibody complexes prepared from the same antigen and intact IgG antibody did not inhibit mitogenesis. None of the mitogens used could be demonstrated to compete with the binding of aggregated immunoglobulin to the B-cell Fc receptor. It appears that the interaction of Fc receptor-bearing lymphocytes and/or macrophages with immobilized complexes prevents lymphocyte activation by mitogens. It is suggested that the mechanism(s) involved may be relevant to antibody feedback control of the humoral immune response.

Animals↗
PubMed1975

Detection of non-H2 antigen(s) which, like Ia antigens, are associated with the Fc receptor of B lymphocytes.

Antibodies contained in an A/J anti-B10 antiserum, when tested on lymphocytes from B10.A mice, were shown to bind to both B and T cells and to inhibit the binding of Ig complexes to the Fc receptors of B lymphocytes. These antibodies could be removed by absorption with B10.D2 lymphocytes. Similar results were obtained with lymphocytes from two to six (B6A)F1 x A/J backcross mice which had H-2a/a genotype. These data indicate that alloantigens determined by at least one non-H-2 locus are associated with or a part of Fc receptors. These antigens may be similar in structure and function to Ia antigens.

Animals↗
PubMed1975

The possible role of i region determined cell surface molecules in the regulation of immune responses.

An hypothetical model has been presented by which I region determined cell surface molecules (Ia antigens) mediate the collaboration between T cells and B cells leading to control of the humoral immune response. The model proposes an analogy between Ia antigens and the constant regions of Ig chains. The absolute requirements of this model are: a) On the B cell the Ia antigen is closely associated with the Fc receptor; b) On the T cell the Ia antigen is closely associated with the product of a linked variable region gene which functions as a specific T cell binding site; and c) The interaction between the T cell Ia molecule and its B cell counterpart leads to B cell activation. By the proposed interactive model no additional Ir gene products are required to explain current concepts of Ir gene function. The experimental evidence from our own laboratory and elsewhere upon which this model is based has been reviewed and a variety of consequences and predictions of the model have been examined. There are numerous aspects of the model which, because of a lack of hard data, are open to alternative explanations. The possible usefulness of this model should lie in its ability to suggest further experiments to elucidate the mechanism of B cell activation and control of the immune response.

Animals↗
PubMed1975

B lymphocytes lacking surface IG in patients with immune deficiency: initiation of IG synthesis in culture in cells of a patient with thymoma.

A 64-year-old woman with a syndrome of thymoma, severe hypogammaglobulinemia, seemingly normal cell-mediated immunity and aplastic anemia, was found to have virtually no immunoglobulin- (Ig) bearing peripheral blood lymphocytes (PBL). However, 7.8 +/- 3.4% of the PBL were positive for another B-cell marker, the receptor for aggregated IgG, while the remaining cells bound sheep erythrocytes. Those cells which were aggregate-reactive appeared to be immature or incomplete B cells. Cultures of peripheral blood leukocytes from the patient in various serum-containing media were studied by 3 independent technics for the development of lymphocyte surface Ig and for Ig in the culture supernatants. In vitro the patient's cells were able to develop surface Ig in media supplemented with fetal calf serum (FCS) or normal serum; in media supplemented with autologous serum, the cells developed no surface Ig. During the cultures in FCS, human Ig determinants became detectable in the medium, and both medium and cell-surface Ig underwent a shift from mu determinants early in the culture period to gamma and alpha determinants later. The development of Ig on the cells was not inhibited by the presence of autologous serum if FCS was included in the medium. These data support the concept that a factor, missing from this patient's serum, is required at an early stage in the maturation of the B cell. A patient with X-linked agammaglobulinemia had a population of circulating lymphocytes with surface characteristics similar to the B cells of the thymoma case. In contrast, no Ig synthesis by this patient's cultured cells could be demonstrated, indicating a different level of block in the 2 cases despite their similarity at the level of the cell surface.

Agammaglobulinemia↗
PubMed1974

Evidence for identity or close association of the Fc receptor of B lymphocytes and alloantigens determined by the Ir region of the H-2 complex.

Immunoglobulin complexes, composed of heat-aggregated human Ig, were shown to bind to mouse B lymphocytes of a variety of strains, but not to either thymocytes or thymus-derived (T) lymphocytes under a variety of conditions. It was shown that this binding was not due to either natural human antibodies against mouse nor to nonspecific binding of human Ig by mouse lymphocytes. Such complexes were shown to bind to the same sites which bind mouse antibody-antigen complexes. This site is known as the Fc receptor. The binding of Ig complexes to mouse B lymphocytes was markedly inhibited by pretreatment of the lymphocytes with anti-H-2 antisera. A series of experiments indicated the specificity of this result, including the fact that this inhibition was shown not to be due to the artifact of shedding of H-2 antibody-antigen complexes, nor to nonspecific steric inhibition. The antibodies within anti-H-2 antisera which were responsible for this inhibition were specific for alloantigens associated with the Ir region of the H-2 complex (Ia antigens). Antiserum specific for these Ia antigens produced inhibition, whereas antisera specific for antigens determined by the K or D regions of the H-2 complex did not. Evidence was obtained using F(1) hybrid cells that at least some Ia antigens of both parental types are expressed on every B lymphocyte (i.e. codominant expression). These data indicate that the Fc receptor and a series of alloantigens controlled by the Ir region of the H-2 complex are identical or closely associated on the B-lymphocyte surface membrane. This observation may have implications for the mechanism of control of the immune response.

Animals↗
PubMed1974

Studies of the human lymphocyte receptor for heat-aggregated or antigen-complexed immunoglobulin.

The lymphocyte receptor for complexed immunoglobulin was shown not to bind heat-aggregated human serum albumin, bovine serum albumin, transferrin, F(ab')(2), reduced and alkylated Ig, and mildly oxidized Ig, which indicated that the receptor is specific for a site dependent on disulfide bond(s) on the Fc portion of complexed Ig. Inhibition experiments provided evidence that the same receptor binds both heat-aggregated Ig and antigen-antibody complexes. Lymphocytes treated with pronase were no longer able to bind Ig complexes, which suggested that the receptor is a protein or glycoprotein. Additional evidence was obtained that lymphocyte surface Ig and the receptor for complexed Ig are distinct since the former could be capped without affecting the distribution of the latter, and surface Ig was not detectable after trypsinization of lymphocytes, whereas the binding of Ig complexes was unaffected by such treatment. Incubation of lymphocytes which had bound Ig complexes in tissue culture medium at 37 degrees C revealed that the complexes remained on the surface membrane for several hours, and that only a minority of lymphocytes binding complexes showed cap formation. Lymphocytes which had heat-aggregated IgG specifically bound to their receptors for complexed Ig were markedly inhibited in their ability to mediate antibody-dependent cytotoxicity, thus providing strong evidence for the necessity of the receptor in this immune activity. Titration of this inhibition with varying amounts of complexes revealed distinct plateaus in the dose-response curve. This suggested that there may be more than one kind of receptor and/or different populations of lymphocytes which bear the receptor.

Animals↗
PubMed1974

Lymphocytes in patients with variable immunodeficiency and panhypogammaglobulinemia. Evaluation of B and T cell surface markers and a proposed classification.

Peripheral blood lymphocytes from 15 patients with variable immunodeficiency and severe panhypogammaglobulinemia were evaluated for B and T cell surface markers. B cells were enumerated by immunofluorescent detection of both surface immunoglobulin (Ig) and the ability to bind aggregated Ig complexes. T cells were identified by their ability to form nonimmune rosettes with sheep red blood cells. Four distinct patterns were observed which were designated types I-IV. Type I: six patients had normal percentages (8.5-19.0%) of Ig-bearing B lymphocytes. Type II: four patients were observed to have B lymphocytes (4.5-15.0%) which lacked fluorescence-detectable surface Ig. Type III: the peripheral blood of these four patients contained a subpopulation (11.3-20.0%) of lymphocytes which apparently lacked both B and T cell markers ("null" cells). Type IV: one patient's blood was characterized by a subpopulation (18.0-22.0%) of lymphocytes which bore both B and T cell markers. Patients of each type had some clinical features in common. It is concluded that evaluation of lymphocyte surface markers provides a means of separating patients with variable immunodeficiency and panhypogammaglobulinemia into distinct groups which appear to differ in the nature of their fundamental defect.

Adolescent↗