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G Möller

Publications and source records attributed to G Möller.

At least 199 records · Page 11Linked to original sources
PubMed1977

Functional heterogeneity of splenic T lymphocyte subpopulations. I. Determination of splenic subpopulations by the use of mitogneic probes.

The results reported here suggest that there exist two T-cell-mitogenic responsive populations in the spleen--one that is responsive to concanavalin A (Con A) and a second one that is responsive to Con A and phytohemagglutinin (PHA). Using an in vitro restimulation system, we have found that a primary in vivo activation with Con A effectively suppresses the subsequent restimulation response to PHA. However, in the reverse experiment, a primary in vivo PHA activation had little effect on the ability of cells to be restimulated with Con A. The suppression seen was due to a refractory recovery period displayed by all cells after previous activation and not to a nonspecific steric hindrance of mitogenic activation receptors due to the lectin remaining on the cell surfaces.

Animals↗
PubMed1977

Polymyxins as inhibitors of polyclonal B-cell activators in murine lymphocyte cultures.

The polymyxin antibiotics polymyxin B sulfate and colistin methane sulfonate were examined for their ability to inhibit responses to the polyclonal B-cell activators (PBA) bacterial lipopolysaccharide (LPS), dextran sulfate (DS), pneumococcal polysaccharide (SIII), and purified protein derivative of tuberculin (PPD) in spleen cell cultures. Polymyxin concentrations of 1 and 10 microng/ml significantly inhibited both the deoxyribonucleic acid synthetic and polyclonal antibody responses stimulated by LPS, DS, and SIII. At these concentrations of polymyxins, responses to PPD and to the T-cell mitogens concanavalin A and phytohemagglutinin were not affected. Inhibition was not caused by a generalized lymphocyte toxicity. After dialysis of LPS-polymyxin and DS-polymyxin mixtures, the PBA preparations showed decreased mitogenic activity. Thus, the polymyxins probably interacted directly with the LPS and DS molecules. The mitogenic response to DS was more significantly inhibited than the response to a nonsulfated dextran. The cationic property of the polymyxins probably allows attachment to negatively charged groups in the mitogenically relevant parts of some but not all PBA molecules,, this attachment resulting in the loss of PBA activity.

Animals↗
PubMed1977

Mitogenic response of mouse spleen cells and gelation of limulus lysate by lipopolysaccharide of Yersinia pestis and evidence for neutralization of lipopolysaccharide by polymyxin B.

Lipopolysaccharide (LPS) extracted with phenol and water from Yersinia pestis was compared with LPS of Escherichia coli for stimulation of deoxyribonucleic acid synthesis in mouse spleen cells (lymphocyte mitogenesis), gelation of limulus lysate, pyrogenicity in the rabbit, and susceptibility to inhibition of these activities by polymyxin B sulfate (PBS). LPS of Y. pestis stimulated deoxyribonucleic acid synthesis in mouse spleen cell cultures over the same quantitative range as LPS of E. coli. In the limulus tests and rabbit pyrogenicity studies, the LPS of Y. pestis was active but about 10 times less potent than E. coli LPS on a weight basis. PBS in concentrations from 1 to 10 microgram/ml diminished the rate of deoxyribonucleic acid synthesis in spleen cell cultures stimulated by LPS of both Y. pestis and E. coli. Addition of PBS to LPS of both Y. pestis and E. coli in a ratio of 100 parts of PBS to 1 part of LPS by weight increased by 10-fold the concentration of LPS required to produce gelation of limulus lysate and inhibited significantly pyrogenic responses in rabbits. These results demonstrating similarities of LPS of Y. pestis and E. coli may suggest that the pathogenesis of plague is similar to that of other gram-negative bacterial infections.

Endotoxins↗
PubMed1977

Evidence for the existence of self-reactive human B lymphocytes.

Supernatants from human tonsil cells cultured in the presence of the PBAs, LPS and F (ab)2 monomers of rabbit anti-human beta2-microglobulin were found to have a complement-dependent cytotoxic activity to tonsil cells of the same donors. A direct toxic effect of the PBAs on the target cells was excluded by controls. Therefore the most likely explanation for this finding is that human lymphocytes contain a subpopulation of self-reactive B cells which can be triggered by PBAs to release antibodies to self-antigens. The implications of this finding for the understanding of infections accompanied by auto-immune phenomena are discussed.

Antibody Formation↗
PubMed1977

Immune response against two epitopes on the same thymus-independent polysaccharide carrier. 1. Role of epitope density in carrier-dependent immunity and tolerance.

Immunogenicity and tolerogenicity of two epitopes (alpha 1-6 and FITC) on the same dextran B 512 carrier were investigated. The following conclusions were made: (1) Both epitopes were thymus-independent and immunogenic and tolerogenic as well. (2) The marked dose differences between the two epitopes with regard to tolerance induction were found to be a consequence of the affinity and the heterogeneity of the responding B cells as well as the epitope density employed for detecting the PFC in a predictable way. (3) The alpha 1-6 response, in contrast to the anti-FITC response, was homogeneous and of low affinity and the number of precursor B cells was low. (4) Different mouse strains were found to be high-, low- or non-responders to alpha 1-6, but all the strains tested responded to the FITC epitope coupled to dextran. (5) Dextran and FITC-dextran were polyclonal B cell activators in the strains tested, irrespective of their ability to respond to the alpha 1-6 epitope. The findings indicate that epitope density and mol. wt of the immunogen as well as Ig receptor affinity for the epitope on the B cells are variables which markedly influence the binding of the immunogen to the specific B cells and therefore affect the delivery of the non-specific triggering signal.

Animals↗
PubMed1976

[Atherosclerosis].

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Arteriosclerosis↗
PubMed1976

Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen.

Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent hapten-protein conjugate as well as by the inability of spleen cells from tolerant animals to respond to a thymus-independent hapten-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to thymus-dependent antigens does not affect B cells, but presumably only T cells. It is suggested that the only stringent test for the existence of B-cell tolerance is the inability of polyclonal B-cell activators to activate antibody synthesis against the tolerogen. The findings make it unlikely that B-cell tolerance to autologous thymus-dependent antigens exists and further indicate that such antigens cannot deliver activating or tolerogenic signals to B cells, although they are competent to combine with and block the Ig receptors.

Animals↗
PubMed1976

Precipitin and mitogenic behavior of dimeric and tetrameric concanavalin A.

The results of double diffusion and quantitative precipitin tests show that in contrast to the concanavalin A tetramer, the dimer is incapable of precipitating glycogen. The results support previous work suggesting that dimers composed of two fragmented monomer units possess only one binding site for carbohydrate (McKenzie and Sawyer, J. Biol. Chem. 1973. 248: 549). On the other hand, dimer and tetramer species had similar mitogenic activity as measured by the incorporation of radioactive thymidine by mouse spleen lymphocytes and induced cap formation to similar degrees. Results are discussed in terms of the affinity and valency of the polymeric forms and their stability at the cell surface.

Animals↗
PubMed1976

Inability of normal and activated thymus-derived cells to act as cytotoxic effector cells against antibody-coated targets.

Thymus lymphocytes activated in vitro by a T cell mitogen (concanavalin A (Con A)) did not form Fc rosettes nor were they cytotoxic against untreated or antiserum-coated target cells. Con A activated spleen cells were cytotoxic against target cells, but they did not display an increased cytotoxic effect against antibody-coated YAC targets, when compared to normal spleen cells. Con A-activated spleen cells as well as cells activated by a mixed lymphocyte culture did not form Fc rosettes. Thus, activated cytotoxic T cells did not form Fc rosettes nor did they cause cytotoxicity on antibody-coated target cells. Antibody coating of the target cells did not suppress expression of cytotoxicity of activated T cells.

Animals↗
PubMed1976

The role of adherent cells in the immune response. Fibroblasts and products released by fibroblasts and peritoneal cells can substitute for adherent cells.

The primary immune response to sheep erythrocytes in adherent cell-depleted cultures was restored by adding a critical number of peritoneal cells. Complete substitution was achieved also with supernatants from allogeneic and syngeneic peritoneal cells. Both living fibroblasts and supernatants from fibroblast cultures were found to be highly efficient substitutes for adherent cells in both syngeneic and allogeneic systems. Supernatants from non-antigen-reated peritoneal cells and fibroblasts caused increased DNA synthesis and induction of polyclonal antibody synthesis in normal spleen cells. Thus, adherent cells need not function in the immune response by presenting antigen to the B cells via 'IgT' or by releasing signal-2 activity, which acts on lymphocytes that have already received signal 1.

Animals↗
PubMed1976

Off-signals in lymphocyte activation.

High-dose unresponsiveness to concanavalin A affected T and B lymphocytes equally, although only T cells were activated by Con A. Thus, activation and inactivation signals are totally unrelated, the latter also lacking target cell specificity. The off-signal caused cell death and is probably biologically unimportant.

Animals↗
PubMed1976

Inhibition of in vitro immune responses by a fraction from seminal plasma.

We studied the inhibitory effect of a fraction of bovine seminal plasma on in vitro lymphocyte responses to specific and nonspecific ligands. Seminal plasma was fractionated by Sephadex G-100 chromatography, and the inhibitory component was found to have a molecular weight of above 100,000 daltons. This fraction was devoid of lymphocytotoxicity and could inhibit, in a dose-dependent mode, both the primary antibody response of normal mouse spleen cells to the thymus-dependent antigen sheep erythrocytes and the one-way mixed lymphocyte reactions. Concanavalin A-induced proliferative T-cell responses were also inhibited by the same fraction. The inhibition of the T-lymphocyte responses to Con A was complete at suboptimal concentrations of the mitogen and could only partially be overcome at supraoptimal concentrations. Four other fractions in seminal plasma were also studied in this particular system, three being without effect and one being stimulatory. The inhibitory fraction was also found to inhibit the polyclonal B-cell responses induced by fetal calf serum. The importance of the present findings for the immunophysiology of reproduction are discussed.

Animals↗
PubMed1976

Lymphocyte-mediated cytotoxicity against tumor cells specificity and characterization of concanavalin A-activated cytotoxic effector lymphocytes.

The selective T cell mitogen Con A was found to induce cytotoxic effectorlymphocytes after in vivo or in vitro treatment. The effector cells exhibited immunologic specificity when tested against tumor cells, killing targets only across H-2 histocompatibility barriers. Thus, Con A caused a polyclonal T cell activation, resulting in the appearance of effector cells capable of recognizing all H-2 antigens, except those coded for by the major histocompatibility loci of the lymphocyte donor. These experiments demonstrate that Con A is capable of activating pre-existing T cells to reveal their genetically determined immunological specificity, and furthermore suggest that there is a deletion of T cell clones with specificity for self. The activated effector cells were characterized as T blasts being relatively insensitive to treatment with anti-O serum plus complement. The precursors of the Con A-activated effector cells were shown to reside primarily in the spleen, to be radio-resistant up to 400 R, and to be short-lived after adult thymectomy. Thus, the population of T cells capable of activation to cytotoxic effector lymphocytes by Con A has similar physical characteristics to the splenic subset(s) of T cells mediating both GVH and cytotoxicity responses upon alloimmunization.

Animals↗
PubMed1975

Role of C'3 and Fc receptors in B-lymphocyte activation.

Attempts were made to identify the non-Ig lymphocyte receptor responsible for B-cell induction by antigen and polyclonal B-cell activators (PBA). As a first step, the role of C'3 and Fc receptors was analyzed. It was shown that complement could be fixed onto B cells to such an extent that the lymphocytes could not bind complement-coated red cells, but this did not result in induction of polyclonal antibody synthesis, nor did it inhibit the lymphocytes response to PBA. However, the C'3 receptros possessed a passive focussing role in the induction of polyclonal antibody responses. Thus, PBA that had fixed complement activated polyclonal responses at lower concentrations than the same substances that had not fixed complement. Most likely the dual binding of PBA molecules to B cells by the PBA and the C'3 receptors caused more PBA molecules to be bound to each cell. However, the focussing function of the C'3 receptors was several orders of magnitude smaller than that of the Ig receptors. Analogous studies were carried out with Fc receptors. Binding of different types of antigen-antibody complexes did not cause activation of polyclonal or specific antibody synthesis, nor did it significantly interfere with induction of antibody synthesis by PBA substances.

Animals↗