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Biomedical subjects

G Möller

Publications and source records attributed to G Möller.

At least 181 records · Page 10Linked to original sources
PubMed1978

Specific antibodies are responsible for the low dose suppression of the immune response to thymus-independent antigens.

Animals primed to the thymus-independent antigen native dextran B512 could not respond to the FITC hapten after immunization with native FITC-dextran. The degree of suppression of the anti-FITC response paralleled the increase of the anti-alpha1-6 PFC after priming with different doses of dextran. Suppression could be passively transferred with serum from dextran primed animals. Young animals that are very low-or non-responders to the alpha1-6 epitope of dextran B512, failed to suppress the anti FITC PFC response after priming with native dextran. We conclude that antibodies against the dextran carrier were responsible for the suppressed response to the FITC epitope in FITC-dextran immunized animals that had been primed with low doses of the dextran carrier.

Animals↗
PubMed1978

Presence of alloantigen-reactive cells in neonatally tolerized mice.

Neonatally induced fully tolerant mice possess cytotoxic effector cells, specific for the tolerizing antigens, which can be induced by polyclonal T cell activators in vivo (Con A) on in vitro (poly A:U). Therefore, clonal deletion of specific effector cells is eliminated as the mechanism by which skin grafts are retained in tolerized mice.

Animals↗
PubMed1978

Immune response to haptenated syngeneic and allogeneic lymphocytes. I. Restrictions for B cell activation by haptenated lymphocytes and specificity of the antibodies generated.

The B cell immune response to altered self was studied using fluoresceinated syngeneic and allogeneic lymphocytes as antigens. Antibody synthesis could be induced in mice injected with syngeneic or allogeneic haptenated lymphocytes as well as heterologous labelled red cells using one particular hapten density. The response to haptenated syngeneic lymphocytes was thymus-independent since nude mice gave a strong response even when the immunogen was FITC-labelled nude cells. The antibodies induced reacted with a complex between a self structure and the hapten, since the best response was detected using FITC-labelled mouse erythrocytes as targets in the plaque assay. These results indicate that a clear distinction must be made between recognition and activation of the responding B cells. The nature of the structures on the modified lymphocyte required to perform these two functions is discussed. It is pointed out that in a dual recognition model of altered self, the duality involved may concern recognition and activation events, rather than two recognition receptors.

Animals↗
PubMed1978

Immunological tolerance to the thymus-independent antigen dextran can be abrogated by thymus-dependent dextran conjugates: evidence against clonal deletion as the mechanism of tolerance induction.

Tolerance to the alpha1--6 epitope of native dextran B512 was found to be very stable and could not be broken by the injection of dextran conjugated to several substances, such as protein A, keyhole limpet haemocyanin, edistin, concanvalin A or Staphylococcus bacteria, strain Cowan. However, when tolerant mice were injected with dextranase, all the above conjugates induced a strong anti-alpha1--6 immune response. In contrast, native dextran itself never induced a response in tolerant, dextranase-treated mice. It was concluded that tolerance only affects the specific B-cell subpopulation that can respond to the polyclonal B-cell-activating (PBA) property of dextran, whereas other specific B cells having PBA receptors for, e.g., signals delivered by collaborating T cells remain in a resting state. These B cells can respond in a specific immune response against the tolerogen after removal of the antigen, which blocks the Ig receptors and therefore prevents them from passively focusing the antigen. Thus, immunological tolerance is not caused by clonal elimination of the antigen-specific clone, but only affects a small subfraction of cells with Ig receptors against the tolerogen.

Animals↗
PubMed1977

Immunological unresponsiveness to thymus-independent antigens: two fundamentally different genetic mechanisms of B-cell unresponsiveness to dextran.

The immune response of mice to the alpha-l-6 epitope of dextran (Dx) B512 was found to be under genetic control. The congenic mouse strains A, A.CA, A.SW, A.TH, and A.TL exhibited a specific defect in their response to alpha-l-6. Also strain CBA/N was unresponsive to alpha-1-6, but the mechanism of unresponsiveness was found to be different. Unresponsiveness to alpha-l-6 in congenic A strains was not due to suppressor cells. Although these strains failed to respond to the alpha-l-6 epitope, they responded strongly to the hapten Fluorescein isothiocyanate (FITC) conjugated to Dx, indicating that the Dx can function as an efficient carrier in these strains. Dx was a potent polyclonal B-cell activator in congenic A strains as well as in high responder strains. Polyclonally-activating concentrations of lipopolysaccharide (LPS) failed to induce the synthesis of anti-alpha- l-6 antibodies in congenic A strains, although antibodies of all other specificities studied were produced. However, in high responder strains, LPS induced the synthesis of anti-alpha-l-6 antibodies. It was concluded that congenic A strains do not express V genes coding for antibodies against alpha-l-6. In contrast, strain CBA/N failed to respond to both the alpha-l-6 and FITC epitope on Dx, whereas they could respond to FITC conjugated to horse erythrocytes. Dx induced a very small, if any, polyclonal antibody response in B cells from CBA/N mice or male CBA/N x DBA hybrids, whereas Dx was a very potent polyclonal B-cell activator in female hybrids. It is concluded that CBA/N mice are nonresponders to Dx or haptenated Dx, because the cell population that can respond to the polyclonal B-cell activating properties of Dx is severely depleted.

Animals↗
PubMed1977

Cytotoxic T-cell activation by polyribonucleotides: DNA synthesis is not required.

We have shown that cytotoxic T cells can be polyclonally activated by a short exposure to complexes of polyadenylic:polyuridylic acid (poly A:U). Activation is optimal at a dose of 100 microgram/ml poly A:U and occurs during a 2 h incubation period in the absence of antigen. Killing of allogeneic, but not syngeneic, target cells can be observed after 12 h in culture and peaks after 21-24 h in the absence of any nonspecific binding ligand. The observed cytotoxicity is mediated by T lymphocytes and dose not require accessory macrophages or DNA synthesis for the activation or expression of effector functions. These results suggest that few requirements exist for the activation of cytotoxic T cells.

Animals↗
PubMed1977

Induction of immunological tolerance requires that the B cells can respond to the polyclonal B-cell-activating properties of the thymus-independent antigens.

Mice were rendered specifically tolerant to the fluorescein isothiocyanatedextran (FITC) epitope by injection of FITC-dextran B512. Their spleen cells were removed at various times and cultivated in vitro with different polyclonal B-cell activators, such as lipopolysaccharide (LPS), purified protein derivative of tuberculin, and native dextran. LPS caused the appearance of high affinity anti-FITC plaque-forming cells to an equal extent with cells from untreated and tolerant animals, whereas native dextran failed to activate cells from tolerant mice, although it was a potent activator of normal cells. It was concluded that tolerance induction only affects those B cells that could respond to the polyclonal B-cell-activating properties of the tolerogen, but not other B cells having an identical set of Ig receptors directed against the tolerogen.

Animals↗
PubMed1977

Experimental conditions for obtaining suppressor and helper effects on the primary in vitro immune response by lymphocytes activated by polyclonal T-cell activators.

The effect of the polyclonal T-cell activators (PTA) Con A and PHA on the specific immune response to sheep red blood cells (SRC) was studied. Addition of PTA either enhanced or suppressed the anti-SRC response, and two variables were found to affect the results: time of addition of the PTA and the strength of the response in control cultures not given PTA. If the response was high, even suboptimal PTA concentrations induced suppressive effects, but if the control response was low, due to deficient batches of sera or because of the absence of serum, the addition of PTA increased the response or restored it to normal levels. Suppression could be obtained if the PTA were added before or at the same time as the antigen and required high (optimal) PTA concentrations. If addition was delayed for 12-24 h the suppressive effects disappeared and previously suppressive concentrations of the PTA now caused an enhanced response. Analogous results were obtained if preactivated lymphocytes were added to the cultures instead of soluble PTA. Neither Con A, PHA, or lymphocytes preactivated by these PTA suppressed the polyclonal response induced by LPS or PPD. Irrespective of the time of addition and the culture conditions, enhancement of the anti-SRC response occurred at lower PTA concentrations than suppression. It was concluded that suppressor T cells, if they exist, do not act on B cells, but rather on helper cells needed for induction of thymus-dependent responses. The findings in this system are not compatible with the existence of a specific subset of suppressor T cells, but rather with the notion that suppression is caused by too much help.

Animals↗
PubMed1977

Characterization of self-reactive B cells by polyclonal B-cell activators.

The existence of autoreactive B cells was predicted by theoretical considerations and, recently, confirmed by direct experiments. The aim of the present work was to investigate if the capacity of self-reactive B cells to be activated with different polyclonal B-cell activators (PBA) reflects the heterogeneity of the response as seen in all the Ig-positive cells. We injected mice with dextran sulfate, lipopolysaccharide from Escherichia coli 055:B5, and purified protein derivate of turbercle bacteria RT32 and studied the complement-dependent cytotoxicity against syngeneic spleen cells caused by the sera from injected mice with regard to the different parameters used for characterization of B-cell subpopulations. It was found that the capacity of self-reactive B cells to secrete antibodies reflects the polyclonal-activating capacity of the PBA used. The implications of these findings for the understanding of the triggering mechanism of B lymphocytes and for self-nonself discrimination are discussed.

Animals↗
PubMed1977

Mechanism of B-cell activation and self-non-self discrimination.

The evidence for the one, nonspecific signal hypothesis, which states that the B lymphocytes are activated by nonclonally distributed receptors which are not the Ig receptors, has been summarized. Even though protein A is a polyclonal B-cell activator, it does not exert its effect by interacting with the Fc part of Ig receptors. One consequence of the one, nonspecific signal concept is that thymus-dependent antigens cannot activate or tolerize B cells. It was shown that B cells from animals tolerant to a thymus-dependent protein antigen could be activated by polyclonal B-cell activators to produce antibodies against the tolerogen. Experimentally induced tolerance did not differ from tolerance to self antigens, since LPS and PPD induced autoantibodies capable of lysing autologous red cells and isotope-labeled autologous and syngenic spleen cells. Thus B cells cannot discriminate self from non-self, whereas T cells have been shown to possess this ability.

Animals↗
PubMed1977

Regulation of in vitro immunocyte activation: origin of and targets for cell-released inhibitors.

Supernatants from incubated normal mouse spleen cells suppressed the DNA synthetic response induced by polyclonal B- and T-cell activators and the primary immune response to sheep erythrocytes in normal spleen cells in vitro. The inhibitory effects of the supernatants were found to be dependent on the culture system used. The main cell population producing or releasing the inhibitory factors was nonadherent spleen cells, but macrophages and bone marrow cells could also give supernatants with inhibitory effects. Thymocytes did not release any inhibitors under the same conditions. Separation of the supernatants showed that there were at least two factors with inhibitory effects on proliferation in lymphocytes. One of these factors had a molecular weight of less than 10,000 (not degradable by protease) and suppressed activation by all tested polyclonal B- and T-cell activators. Another factor (a protein with a molecular weight of more than 30,000) inhibited activation by some polyclonal B-cell activators (lipopolysaccharide, type III pneumococcal polysaccharide) whereas the proliferation induced by dextran sulfate was less or not at all affected under the same culture conditions. Trivial mechanisms for inhibition by supernatant factors, such as medium depletion, general toxicity, and accumulation of free thymidine in the medium, were excluded.

Animals↗
PubMed1977

Polyclonal antibody secretion in human lymphocytes induced by killed staphylococcal bacteria and by lipopolysaccharide.

Preparations of Staphylococcus aureus strains Cowan 1 and Wood 46 and of lipopolysaccharide (LPS) were found to act as polyclonal B-cell-activating substances for human splenic and blood lymphocytes. All three substances induced polyclonal antibody secretion in blood and spleen cell cultures, as tested against fluorescein isothiocyanate-coupled sheep erythrocytes by a modification of the local hemolysis-in-gel assay. Antibodies were of IgM class, as shown by inhibition of plaque formation by anti-IgM but not by anti-IgG or anti-IgA antisera. All these substances also consistently induced the formation of intracellular immunoglobulin and increased DNA synthesis in stimulated spleen cells. In blood lymphocytes Staph. aureus Cowan 1 induced a consistent increase in DNA synthesis, whereas Staph, aureus Wood and LPS often gave low or no increase in DNA synthesis. Peak antibody formation was observed on day 3 in spleen cells and on day 6 in blood lymphocyte cultures. Stimulation into high-rate immunoglobulin secretion occurred with all PBAs also in B-cell-enriched cell suspensions but not in T-cell-enriched cells. Optimal responses were, however, always noted in unseparated cell suspensions. It is concluded that preparations of killed bacteria can be useful tools for the clinical evaluation of both specific and nonspecific antibody-forming ability in cells from different groups of patients.

Antibody Formation↗
PubMed1977

Mechanism of action of suppressor cells. In vivo concanavalin-A-activated suppressor cells do not directly affect B cells.

The addition of a small proportion (10%) of in vivo concanavalin-A (Con-A)-activated spleen cells to normal spleen cell cultures suppressed the primary immune response to sheep erythrocytes (SRBC) but had no effect on the thymus-independent primary immune response to 3,5-dinitro-4-hydroxy-phenacetyl-conjugated lipopolysaccharide. When Con-A-activated cells were added after 24 h, there was no suppression of the anti-SRBC response but rather an enhanced response when few cells were admixed. Con-A-activated cells did not influence activation of normal cells by polyclonal T- and B-cell activators. It is concluded that Con-A-induced suppressor cells do not act on B cells but rather on helper cells (T cells or macrophages) at a very early stage of the immune response to thymus-dependent antigens.

Animals↗
PubMed1977

The polyclonal B-cell-activating property of protein A is not due to its interaction with the FC part of immunoglobulin receptors.

Protein A from Staphylococcus aureus bacteria was found to be a B-cell mitogen and a potent polyclonal B-cell activator (PBA) of antibody synthesis for murine lymphocytes in the absence of macrophages or T lymphocytes. It did not activate T lymphocytes. We investigated whether the interaction between protein A and the Fc part of Ig molecules was responsible for the PBA activity. Protein A failed to induce IgG synthesis in spleen cells from normal mice, even though it binds effectively to IgG molecules. Lymphocytes treated with anti-immunoglobulin antisera followed by protein A were not activated to a larger extent than non-pretreated cells, although only the former cells bound protein A. Finally, direct attempts to suppress the PBA property of protein A by blocking the Fc binding ability with serum or human gamma globulin failed. We concluded that protein A possesses two separate biological properties, namely to interact with the Fc receptor on Ig molecules and to act as a PBA, and these properties are carried out by different parts of the molecule. These findings confirm previous failures to find an active role of the Ig receptors on B lymphocytes in the triggering process.

Animals↗