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Biomedical subjects

G Möller

Publications and source records attributed to G Möller.

At least 109 records · Page 6Linked to original sources
PubMed1989

Regulation of IgG1 and IgE synthesis by interleukin 4 in mouse B cells.

Mouse interleukin 4 (IL-4) has been shown to act on B cells as an induction factor for Ig class switch. We studied the characteristics of IL-4-regulated Ig isotype production in lipopolysaccharide (LPS)-stimulated splenic B-cell cultures with emphasis on the comparison between the IgG1 and IgE responses. The results show that the kinetics for the appearance of IgG1 and IgE isotypes are similar, but that the dose of IL-4 required for the induction of an IgE response is 3-10 times higher than that for an IgG1 response. No requirement for T cells was found for the induction of either isotype. Pre-incubation of cells for 24 h with IL-4 alone was sufficient to induce an IgG1 response when cells were recultured with LPS from days 1 to 6. However, the simultaneous presence of both IL-4 and LPS for at least 24 h was required for a detectable IgE response. For an optimal IgE response, IL-4 needed to be present for more than 72 h in LPS-activated cultures. The possible reasons for the different regulation of IgG1 and IgE responses are discussed.

Animals↗
PubMed1989

Capping and co-capping of membrane immunoglobulin and lipid-conjugated immunoglobulin inserted in the cell membrane of B lymphocytes.

Human and mouse immunoglobulins (Ig) or F(ab')2 fragments of rabbit Ig were conjugated to lipids and the conjugates inserted into the membrane of mouse spleen cells. It was found that nearly all B cells, but not T cells, became decorated with lipid immunoglobulin. Both endogenous Ig receptors and inserted Ig capped after the addition of cross-linking F(ab')2 antibodies and in both cases capping required energy. Capping of endogenous mouse Ig led to co-capping of inserted human Ig, but the reverse was not true.

Animals↗
PubMed1989

Forced contact between antigen-presenting cells and T cells: consequences for T-cell activation.

It is still not known how T cells are activated, which T-cell surface structures transmit activation signals, and if antigen-presenting cells possess activation structures for T cells. We have studied whether the T-cell receptor (TcR) must be engaged for T-cell activation to occur. By using membrane-incorporated monoclonal antibodies, we artificially forced T cells to bind to antigen-presenting cells in a mixed lymphocyte reaction system and thereby bypassed the need for TcR engagement and also made it possible for any surface molecule on antigen-presenting cells to deliver a stimulatory signal to the T cells. Theoretically, T cells would become polyclonally activated by this procedure. However, we found that they did not, even though they were intimately bound to the antigen-presenting cell, thus demonstrating that the TcR must participate in antigen/MHC binding in order for the T cells to become activated. This study does not exclude the possibility that antigen-presenting cells possess structures that can activate T cells.

Animals↗
PubMed1989

Rheumatoid synovial fluid reconstitutes the B-cell defect in CBA/N mice.

Synovial fluid from patients with rheumatoid arthritis (RA-SF) contains a biological activity which can replace T cells for activation of antibody secretion in human blood lymphoid cells and which can also induce the selective differentiation of IgG2b-secreting cells in lipopolysaccharide (LPS)-pre-activated mouse spleen cells. The B-cell activity of this factor was studied in CBA/N mice which have an X-linked B-cell immunodeficiency which manifests itself as a defective humoral response to certain thymus-independent antigens (TI-2). RA-SF has now been shown to reconstitute partly the B-cell deficiency in CBA/N splenic B cells in vitro. Addition of RA-SF to LPS-pretreated cell cultures results in IgG2b secretion in CBA/N spleen cells as well. In contrast to cells from normal CBA mice, cells from CBA/N mice cannot respond to interleukin 4 (IL-4) after addition of LPS with production of IgG1 antibodies in vitro. However, the addition of RA-SF completely restores a normal IL-4-induced IgG1 response. No other biologically active factors have been shown to allow the production of IgG antibody producing cells in CBA/N splenic B cells. It is postulated that the xid immunodeficiency could be the result of a deficient production of a biological activity which is abundant in RA-SF.

Animals↗
PubMed1989

Autoantibody formation after bone marrow transplantation. Comparison between acetylcholine receptor antibodies and other autoantibodies and analysis of HLA and Gm markers.

Clinical myasthenia gravis has been reported in an increased frequency after bone marrow grafting. The number of bone marrow transplanted patients making IgG autoantibodies directed against the autoantigens cardiolipin, SS-B (La) and thyroglobulin was found to be significantly lower as compared to the autoantigen acetylcholine receptor protein. The occurrence of antibodies to single-stranded DNA was found in a lower frequency than acetylcholine receptor antibodies but the difference was not statistically significant. Antibodies to cardiolipin were frequently observed prior to grafting. The G1m1,2 and G3m5 phenotype frequency did not differ in individuals who developed receptor antibodies from that found in the normal population. Analysis of HLA antigens in this patient group revealed no association to HLA B8/DR3 or B35/DR1. This may indicate that the etiology of myasthenia gravis induced by bone marrow grafting differs as compared with the spontaneous form of myasthenia gravis and the penicillamine-induced disease.

Antibody Formation↗
PubMed1989

[Objective estimation of the motility of deep frozen cattle sperm by videomicrography and computer image analysis].

It was examined whether computerized image analysis (system "Brunner") is suitable for the objective evaluation of the quality of deep-frozen bull sperm obtained from the routine of breeding stations. Egg yolk particles similar in size to sperm heads were classified as immotile sperm. Thus, motility was significantly underestimated with the degree of underestimation depending on the thawing solution employed. The use of two different thawing solutions, CUE and Citrat-Glucose, resulted in significantly different sperm motion characteristics immediately after thawing as well as at the end of a 2 hour incubation period at 37 degrees C. Deep-frozen semen samples from seven bulls were compared with respect to their swimming activities. The rank order of the bulls based on the values for motility and mean velocity measured two hours post-thaw corresponded with the rank order of Non-Return-Rates with respect to bulls from the same breeding station. It appears that the combination of videomicrography and computerized image analysis is well suited for the objective evaluation of frozen-thawed bull sperm if the extender is pretreated to exclude an underestimation of motility caused by egg yolk particles.

Animals↗
PubMed1988

Enumeration of IFN-gamma-producing cells by flow cytometry. Comparison with fluorescence microscopy.

A new intracytoplasmic immunofluorescence staining to detect and quantify human interferon-gamma (IFN-gamma)-producing cells by means of flow cytometry is described. Mononuclear leukocytes, stimulated in vitro to produce IFN-gamma, were fixed and made permeable to antibodies by sequential exposure to paraformaldehyde and the detergent n-octyl-glucoside. Cytoplasmic IFN-gamma was demonstrated by indirect immunofluorescence using IFN-gamma-specific mouse monoclonal antibodies. The staining exhibited a very characteristic morphology and was localized in the Golgi apparatus. An excellent agreement between the enumeration of cytoplasmic IFN-gamma-positive cells by immunofluorescence microscopy and flow cytometry was noted. However, the latter has the advantage of a standardized control, is less labor consuming and is observer independent.

Adult↗
PubMed1988

Anti-alpha 1-6 epitope, specificity of a T-cell hybrid-secreted factor: affinity- and ion-exchange chromatographic separation.

We have studied the specificity of the products of a "T-cell" hybridoma, Th 1, a fusion product of AKR thymoma BW 5147 with spleen cells from Dx-hyperimmunized mice, which has been shown to affect the anti-Dx but also the anti-SRC response from culture supernatants and ascitic fluids. The anti-Dx-affecting material was separated from unspecific effector molecules by Sephadex affinity chromatography combined with HPLC DEAE chromatography and gel filtration. The activities of fractions were tested for their effects on anti-Dx, anti-SRC, and anti-SSS-III IgM responses. We show that the anti-Dx response-affecting material binds to Sephadex. Its Ig contamination can be reduced by two DEAE chromatographies at pH 6 and 8.1. At pH 8.1 it starts eluting with 0.13 M NaCl, but is still contaminated with materials that affect the anti-SRC and to a smaller extent the anti-SSS-III response. On gel filtration it localizes in the area of 100-40 kDa. The effects of the active material on anti-Dx IgM varied from suppression to enhancement. The details of that effect are largely unknown but three other findings further confirm the Dx specificity of Th 1 products. The growth of Th 1 in mice induces the production of anti-Dx IgA, detectable in their sera with ELISA. The priming of mice with Th 1 products affects the magnitudes of anti-Dx IgM PFC responses to the subsequent immunization with Dx with or without the product. The binding to Dx of material from in vivo active fractions can be verified in the ELISA with an antiserum produced against Th 1.

Animals↗
PubMed1988

Interleukin 4 instructs uncommitted B lymphocytes to switch to IgG1 and IgE.

Mouse interleukin 4 (IL 4) is a T cell-produced lymphokine with multiple effects on different cells types of the hematopoietic lineages. IL 4 has pronounced effects on B lymphocytes, where it induces high levels of IgG1 and IgE secretion in lipopolysaccharide-stimulated cultures that would otherwise secrete predominantly IgG3 and IgG2b (of the non-IgM isotypes). An important question is how IL 4 exerts its effect. Two main possibilities exist: (a) IL 4 instructs uncommitted B lymphocytes to IgG1 and IgE production; (b) IL 4 selects and expands an already precommitted B cell. In this study we show, by the use of limiting dilution analysis, that IL 4 dramatically increases the precursor frequency of IgG1 and IgE-secreting cells with no significant effect on the clone size, clearly suggesting that IL 4 instructs uncommitted B cells to switch to IgG1 and IgE. The fraction of total Ig precursors that can switch to the two isotypes is furthermore high. The high precursor frequency for IgE obtained in the presence of IL 4 further demonstrates that IL 4 is an important modulator of IgE responses.

Animals↗
PubMed1988

Concomitant production of different lymphokines in activated T cells.

The intracellular accumulation of five different lymphokines in individual cells could be identified by lymphokine-specific antibodies and an indirect immunofluorescence technique with UV microscopy. When peripheral blood mononuclear cells from one healthy donor were activated in vitro by the T cell mitogen anti-CD3 monoclonal antibody, the maximal number of cells producing interleukin (IL)2, IL 6 or tumor necrosis factor (TNF)-alpha occurred 6 h after initiation of the cultures, while peak numbers of interferon-gamma, TNF-beta and a second wave of TNF-alpha-synthesizing cells were noted approximately 20 h later. By performing two-color immunofluorescence studies we observed a variegated production pattern with cells making no, one or several lymphokines simultaneously. All five cytokines accumulated in the Golgi organelle resulting in a very characteristic morphology of the staining with or without additional cytoplasmic immunofluorescence.

Antibodies, Monoclonal↗
PubMed1988

Immune response in deep cervical lymph nodes and spleen in the mouse after antigen deposition in different intracerebral sites.

Brain interstitial and cerebrospinal fluid drainage into the lymphatics was studied by injections of 5 microliters of packed sheep red blood cells (SRBC) injected into the caudate nucleus, the occipital lobe, and the lateral ventricle of the brain in mice. The number of plaque-forming cells (PFC) was determined in the deep cervical lymph nodes, the axillary lymph nodes, and the spleen, and the number of PFC was compared with the response in the same tissues after intravenous immunization with 0.1 ml 10% SRBC. The weight of the deep cervical lymph nodes increased 3.0 times on day 3 after injection in the brain parenchyma compared with the weight of these nodes after intravenous immunization. The antigen-specific response peaked on day 5, 392 +/- 37 PFC/10(6) for IgG in the deep cervical lymph nodes after antigen deposition in the caudate nucleus, whereas only a minor peak in the antigen-specific response was obtained after intraventricular antigen deposition, 127 +/- 79 PFC x 10(6) for IgG on day 6. There were no increased PFC in any of the lymph nodes after intravenous immunization. The experiments show an antigen-specific response in the deep cervical lymph nodes after intracerebral antigen deposition, whereas antigens deposited in the lateral ventricles drain preferentially to the blood, with a high response in the spleen.

Animals↗
PubMed1988

Antigen-antibody complex-induced immunosuppression. Effect of F(ab')2 antibodies and protein A.

The addition of immune complexes (anti-horse red blood cell (HRC) antibodies plus HRC) to spleen cell cultures activated by lipopolysaccharide (LPS) selectively suppressed the anti-HRC plaque-forming cell (PFC) response, but did not affect the PFC response to sheep red blood cells (SRC). The degree of suppression was directly related to the concentration of immune complexes. F(ab')2 preparations suppressed as efficiently as intact IgG, although the ability of the F(ab')2 preparation to lyse the red cells was abolished. The addition of protein A to the immune complexes (using intact antibodies) did not affect the degree of suppression. The findings suggest that immune complex-induced suppression of polyclonal B cell activation is caused by constant parts of the light or heavy chains of the antibodies other than the Fc part.

Animals↗
PubMed1988

Lipopolysaccharide as a tool to reveal autoreactive B cells.

It has been found in several different test systems that LPS is competent to induce autoantibodies of different specificities. As a rule only IgM autoantibodies have been found. The presence of autoreactive B cells in healthy individuals indicate that autoreactive B cells have not been not eliminated by the induction of immunological tolerance. This result is to expected according to the concept of the one non-specific signal hypothesis for B cell activation, which only ascribes a passive focussing role to the immunoglobulin receptors, whereas activation and tolerogenic signals are delivered via non-clonally distributed receptors for polyclonal B cell activators and T cell interleukins. The induction of autoantibodies by LPS in mice does not result in detectable disease or symptoms. Therefore, the ability of LPS to induce IgM autoantibodies does not constitute a model for induction of autoimmune diseases. The main importance of these findings is that the self-non-self distinction is not carried out by B cells. Presumably T cells alone are responsible for the self-non-self distinction.

Animals↗
PubMed1988

The antibody spectrum in individuals with defect expression of HLA class II and the LFA-1 glycoprotein family genes.

HLA class II antigens and the LFA-1 (lymphocyte function-associated type 1) glycoprotein family are cell surface structures of central importance in many lymphocyte reactions. Specific antibodies are normally restricted to particular IgG subclasses. In order to study the mechanism of isotype restriction we have analysed specific IgG1, IgG2, IgG3 and IgG4 antibodies directed against a number of different protein and polysaccharide antigens in individuals with HLA class II or LFA-1 deficiency. HLA class II deficiency resulted in decreased total IgG2, IgG4 and IgA in 4/4 patients, whereas total IgM and IgG were low in 2/4. In HLA class II deficiency the levels of specific antibodies directed against protein as well as polysaccharide antigens were frequently low. Virtually normal total as well as specific antibody levels were found in individuals with both severe and moderate forms of LFA-1 deficiency. There was no clear evidence for an abnormal subclass pattern of specific antibodies with a shift from one subclass to an isotype which is normally not used, in any of the patient groups investigated.

Adult↗
PubMed1987

Regulation of the antibody response to sheep erythrocytes by monoclonal IgG antibodies.

Monoclonal antibodies directed against sheep erythrocytes of the isotypes IgG1, IgG2b and IgG2a were used to analyze the specificity of antibody-induced suppression of the immune response. It was first shown that all monoclonals reacted against different antigenic determinants and they all suppressed the immune response to sheep erythrocytes when given shortly after the antigen to more than 50% as compared to 90-96% inhibition obtained with a polyclonal antiserum. Increasing the doses of monoclonals did not increase suppression. However, two different monoclonals administered together caused an additive, but not a synergistic inhibitory effect. No enhancement of the immune response was observed with any of the Ig classes tested. These findings show that four different antigenic determinants on sheep erythrocytes induced the synthesis of corresponding antibodies, with little or no signs of a dominant determinant. Passively administered monoclonal antibodies, even at supraoptimal doses, never suppressed the immune response to the same extent as a polyclonal antiserum, suggesting that each monoclonal only suppressed the synthesis of the corresponding antibody and did not affect antibody synthesis to other determinants.

Animals↗