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Biomedical subjects

G Möller

Publications and source records attributed to G Möller.

At least 163 records · Page 9Linked to original sources
PubMed1980

Suppression of the immune response to altered self induced by immunogenic and nonimmunogenic altered self structures.

Fluorescein (FITC)-haptenated mouse spleen cells are capable of inducing a B cell immune response characterized by the production of antibodies directed against hapten-altered self structures. The induction of this response is thymus-independent and strictly dependent on the hapten concentration used for labeling the cells. Pretreatment of mice with immunogenic, labeled spleen cells strongly suppressed the plaque-forming cell response to a subsequent challenge with FITC-labeled spleen cells, sheep (SRC) or horse (HRC) red cells labeled with the same hapten and native FITC-dextran. Mice primed with lightly haptenated (nonimmunogenic) cells 7 days before challenge were completely unresponsive to the immunogenic dose of labeled cells and displayed a significantly reduced response to FITC-SRC or FITC-HRC. However, the response to FITC-dextran was enhanced, as compared to unprimed animals. The concept of immunogenic vs. nonimmunogenic requirements of an antigen to induce unresponsiveness, and the specificity of the B cell clones affected by suppression is discussed.

Animals↗
PubMed1980

Pion dosimetry with thermoluminescent materials.

Various thermoluminescent materials (6LiF, 7LiF, Li2B4O7:Mn, CaSO4:Dy, CaF2:Mn, CaF2-Dy, CaF2:Tm) were irradiated with pi- mesons throughout the depth dose distribution of a beam with central momentum of 176 MeV/c. Doses from 0.05 to 2 Gy were used and linearity and reproducibility were investigated. For LiF, CaF2:Dy and CaF2:Tm, low- and high-temperature peaks were analysed separately. CaF2:Tm was found to be the most suitable for pi- dosimetry since the total dose and the high LET component could be determined using the integral TL signal and the peak height ratio of the 150 degrees C and 240 degrees C peaks. In the dose range used, both peak responses are linear with dose and the sensitivity of the materials is 10 times that of LiF. The reproducibility was +/- 3%. The high temperature peak of 7LiF is too small to be determined accurately and the high temperature peak of CaF2:Dy decreases with increasing LET in the same way was the low temperature peak does, so that no LET information can be extracted.

Calcium Fluoride↗
PubMed1980

A primary immune response to dextran B512 is followed by a period of antigen-specific immunosuppression caused by autoanti-idiotypic antibodies.

After a primary immune response to the alpha 1-6 epitope of dextran B512, dextran high responder strains exhibit a specific inability to produce IgM and IgG antibodies against this epitope, although they gave an expected secondary response to horse erythrocytes. Spleen cells from dextran-primed and-suppressed mice responded well to dextran after transfer to lethally irradiated previously untreated mice, indicating that tolerance or exhaustive proliferation of dextran reactive B cells is not responsible. Thymus-dependent dextran-protein conjugates also induced specific suppression. Suppression to both dextran and horse erythrocytes could be passively transferred into untreated recipients with immune serum. However, after absorption with horse erythrocytes and dextran, passive serum transfer only suppressed the response to dextran. It is suggested that the specific immunosuppression was caused by the appearance of autoanti-idiotypic antibodies directed against the immunoglobulin receptors of dextran-reactive B cells.

Animals↗
PubMed1980

Antibody-coated sheep erythrocytes suppress the ability of polyclonal B-cell activators to induce plaque-forming cells against sheep erythrocytes.

The primary immune response to untreated sheep erythrocytes (SRBC) in vitro was suppressed by the addition of antibody-coated SRBC. A mixture of SRBC and antibody-coated SRBC also suppressed the induction of anti-SRBC plaque-forming cells by the polyclonal B cell activators lipopolysaccharide, purified protein derivative of tuberculin, and native dextran. Injection of a mixture of SRBC and antibody-coated SRBC into mice led to an increased response to SRBC. It seems plausible from the in vitro findings that the Fc part of antibodies complexed to an antigen can exert a negative signal on antigen-specific B cells that cannot be overcome by positive signals delivered by polyclonal B cell activators.

Animals↗
PubMed1980

Binding characteristics of aggregated IgGa to rat basophilic leukaemia (RBL) cells and rat mast cells.

The binding properties of h. a. IgGa to the Fc-gamma receptor on rat basophilic leukaemia cells and rat mast cells were analysed. When h. a. IgGa was coupled to SRBC, rosette formation was observed with normal mast cells as well as with cells obtained from Nippostrongylus brasiliensis-infected rats. The binding of aggregates was detected by fluorescent analysis. With monomeric IgGa, no uptake was observed. Binding analysis was also performed with aggregates of different sedimentation coefficients varying from 10S to 130S. It was demonstrated that h. a. 125I-IgGa binds to rat mast cells as well as to RBL cells. The rate of binding is dependent on the number of Fc portions present within the aggregate. Pre-incubation of aggregates with protein A partially inhibited the subsequent binding. The binding of aggregates is more potent at 37 degrees, increases by five-fold at pH 6.4 as compared to pH 7.4 and is reduced by 75% at pH 8.4, while the binding of 125I-IgE did not differ at the various pH values. In the presence of Ca2+ ions, a 30-40% increase in the uptake of aggregates was noted. Our results show the presence of Fc-gamma-receptors on RBL-cells and rat mast cells by direct binding studies and suggest molecular differences of the Fc-gamma and Fc-epsilon receptors.

Animals↗
PubMed1979

Antigen-induced strain-specific autoantiidiotypic antibodies modulate the immune response to dextran B 512.

Sera from CBA and C57BL mice immunized against dextran B 512 eight or more days earlier contain mainly IgG antibodies that specifically suppress the development of plaque-forming cells against dextran in vitro. Suppression was not caused by antibodies against the alpha 1-6 epitope of dextran to any major extent. Sera from CBA mice (IgCH allotype j) suppressed plaque-forming cells from CBA mice, whereas sera from C57BL mice (allotype b) inhibited plaques from C57BL and CBA/Ig-1b mice. Sera from dextran-tolerant mice or from mice that are genetic unresponders to dextran did not suppress plaque-forming cells. Both thymus-independent and thymus-dependent forms of dextran induced the appearance of these autoantiidiotypic antibodies that can distinguish between anti-alpha 1-6 antibodies produced in mouse strains having different IgCH-locus-determined allotypes.

Animals↗
PubMed1979

The immune response to the alpha 1-6 epitope of dextran is determined by a gene linked to the IgCH locus.

There is a marked strain variability in the immune response against the alpha 1-6 epitope of dextran B512. Responsiveness was independent of the H-2 genotype of the strains but completely determined by the IgCH allotypes of the strains. Thus, IgCHb and IgCHj allotypes characteristic of C57BL and CBA strains, respectively, determined high responsiveness, whereas strains possessing all other allotypes studied were low responders. Backcross analysis indicated that a gene(s) determined responsiveness and that this gene was linked to allotypes of the IgCH locus. F1 hybrids between high and low responder strains always gave a response, but the number of plaque-forming cells was approximately half of that obtained in the high responder strains.

Animals↗
PubMed1979

A thymus-independent IgG response against dextran B512 can be induced in C57BL but not in CBA mice, even though both strains possess a VHdex gene.

CBA and C57BL mice both possess a VHdex gene coding for antibodies against the alpha 1-6 epitope of dextran B512. After immunization with dextran, CBA mice produce IgM plaque-forming cells (PFC) only, which show regular cyclical fluctuations. The second PFC peak disappeared after injection of dextranase, indicating that it is antigen-dependent. The anti-dextran response in C57BL mice is characterized by only one IgM peak, followed 1 day later by an IgG peak that may exceed the IgM response by a factor of 10. The IgG anti-dextran response in C57BL mice was thymus-independent. CBA mice gave an IgG response to the hapten fluorescein isothiocyanate (FITC) after immunization with FITC-dextran, indicating that dextran can function as a carrier for an IgG response in this strain. Attempts to induce IgG PFC against dextran by immunizing CBA mice with thymus-dependent dextran-protein conjugates consistently failed, althouth the conjugates induced IgG fc in C57BL mice. Spleen cells from CBA mice failed to produce IgG antibodies against dextran after transfer into lethally irradiated C57BL mice, whereas the C57BL spleen cells produced IgG PFC after transfer into CBA mice. The lack of IgG synthesis against the alpha 1-6 epitope of dextran in CBA mice appears to be regulated exclusively at the B cell level and is restricted specifically to the VHdex gene product.

Animals↗
PubMed1979

Bacterial lipopolysaccharides bind selectively to lymphocytes from lipopolysaccharide high-responder mouse strains.

Three different concentrations of horseradish peroxidase-labelled lipopolysaccharide (LPS-HRP) were added in vitro to spleen cells from the LPS high-responder strain C3H/Tif and to cells from the low-responder strain C3H/HeJ. After being washed and fixed the cells were exposed to the substrate and prepared for electron microscopy. After addition of 7 and 0.7 microgram/ml of labelled LPS only lymphocytes from the high-responder strain were labelled. About 5-10% of the cells from C3H/Tif bound LPS, which is in accordance with the known frequency of B cells possessing the genetically determined LPS receptor. At the highest dose of labelled LPS (70 microgram/ml) a large proportion of lymphocytes from the low-responder strain also bound LPS. Erythrocytes from both strains bound LPS at all concentrations. It is concluded that LPS-HRP allows the detection at the cellular level of LPS binding to the genetically controlled membrane receptor for LPS.

Animals↗
PubMed1979

Con-A-activated T cells secrete factors with polyclonal B-cell-activating properties.

Concanavalin A induced polyclonal antibody synthesis in normal spleen cells in vitro. Optimal responses were obtained by Con A concentrations lower than those optimal for induction of DNA synthesis. T cells, but not macrophages, were necessary for the effect. Spleen cells from nude mice were not activated, whereas cells from the LPS non-responder stain C3H/HeJ were activated to polyclonal antibody synthesis by Con A. Supernatants from Con A activated spleen cells could by themselves induce polyclonal antibody synthesis in untreated spleen cell cultures, even when Con A had been removed by absorption with Sephadex G-50 and when alpha-methyl-mannoside was present in the secondary cultures. T cells produced the active supernatants, which were competent to induce polyclonal antibody synthesis, but not DNA synthesis, in both H-2-incompatible and compatible strains. When the supernants were absorbed with erythrocyte antigens, they specifically induced an enhanced response, in secondary cultures, to the antigen used for absorption. Possible mechanisms of this specific effect are discussed.

Animals↗
PubMed1978

Immunological unresponsiveness to native dextran B512 in young animals of dextran high responder strains is due to lack of Ig receptors expression. Evidence for a nonrandom expression of V-genes.

Young mice of dextran high responder strains were found to be complete nonresponders to the alpha-1-6 epitope of dextran during 30-40 days after birth. They also failed to respond to thymus-dependent dextran-protein conjugates. Cells from young and adult mice were activated equally well to polyclonal antibody synthesis by the polyclonal B-cell-activating property of dextran. There was no age difference in the immune response to haptens conjugated to dextran, indicating that dextran can function as an efficient carrier also in young mice. Unresponsiveness could not be attributed to suppressor T cells or to a suppressive environment in young animals, as shown by transfer experiments, in which living or irradiated cells from young and adult mice were admixed in various ways and transferred to irradiated recipients of different ages. Cells from young mice did not affect response of adult cells (and the reverse), nor did the age of the irradiated recipient influence the response. When lymphocytes from young and adult mice were polyclonally activated in vitro by lipopolysaccharide, only cells from young mice failed to synthesize antibodies against the alpha-1-6 epitope of dextran, although they produced antibodies of all other specificities tested for. It was concluded that young animals fail to express immunoglobulins directed against the alpha-1-6 epitope during the first 30-40 days after birth. Since the mice possess the VH gene coding for antibodies against this particular epitope, it was concluded that the timing of V gene expression is regulated during development, possibly at the V-C gene translocation level.

Aging↗
PubMed1978

Irreversible immunological tolerance to thymus-independent antigens is restricted to the clone of B cells having both Ig and PBA receptors for the tolerogen.

Mice were tolerized to the alpha1-6 epitope of native dextran. When their spleen cells were removed and activated by LPS, they did not synthesize antibodies against the tolerogen. However, when cells from tolerant mice were treated with dextranase or left untreated in culture for 24 h they were activated by LPS to the synthesis of antibodies against the tolerogen. When 24 h tolerized lymphocytes were treated with dextranase and transferred with immunogenic doses of dextran to irradiated mice they failed to produce antibodies against the tolerogen. In contrast, cells incubated with dextran for 2 h and thereafter dextranase treated were readily immunized by dextran in the same system. It is concluded that only the B cell clones having both Ig receptors and PBA receptors for the tolerogen become irreversibly tolerized, whereas B cells having Ig receptors for a different PBA are not tolerized, but remain in a resting state, even though their Ig receptors have bound the tolerogen.

Animals↗
PubMed1978

The polyclonal B cell activator dextran-sulphate induces formation of colony stimulating activity.

The effect of dextran-sulphate (DS), a polyclonal activator known to stimulate immature murine B-cells, was assayed in a culture system allowing the growth of myeloid cells. It was known that DS induced the production of a myeloid colony stimulating factor (CSF) by cells from both spleen and bone marrow. Nylonwool purified mouse spleen cells, enriched for T cells, showed a dimished CSF production in response to DS, while CSF production in response to Con A was increased. Furthermore, DS induced CSF in both spleen and bone marrow cells from nude mice. Removal of macrophages did not affect CSF production. The CSF induced was non-dialysable and no small molecular weight or lipoprotein inhibitors could be demonstrated. The results suggest that DS activates cells other than T cells or macrophages (possibly B cells or null cells) to produce a myeloid stem cell stimulating substance. These results indicate that interactions between lymphoid and myeloid cells can take place during differentiation.

Animals↗