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G Möller

Publications and source records attributed to G Möller.

At least 217 records · Page 12Linked to original sources
PubMed1975

Factors influencing activation of B-cells in immunity.

The hypotheses so far advanced for B-cell activation by antigen are based on the assumption that the interaction between antigen and the Ig receptors delivers at least the initial triggering signal. There are few, if any, experimental findings to support this assumption. On the contrary, a variety of findings indicate that the Ig receptors do not deliver any signal to the cells, whereas activation can be regularly achieved without participation ofIg receptors. The available evidence forces us to suggest that antigen-induced B-cell triggering is always caused by one nonspecific signal, which is delivered to the cells by surface structures, which are not the Ig receptors. For distinctive features of this hypothesis see One Nonspecific Triggering Signal. Various competing hypotheses for B-cell activation have been analyzed, but none of them appears to satisfy the experimental findings.

Animals↗
PubMed1975

Mechanism of b-lymphocyte activation: failure to obtain evidence of a direct role of the Ig receptors in the triggering process.

Experiments were designed to test two hypotheses of B-cell activation by antigen: the cross-linking concept, postulating that a suitable degree of antigen-induced cross-linking of the Ig receptors is sufficient for immunocyte triggering, and the two-signal hypothesis, suggesting that a first signal delivered by antigen interacting with the Ig receptors followed by a second signal given by, for example, a polyclonal B-cell activator is necessary for activation. The results did not support either of these hypotheses. Thus, the hapten FITC coupled to human serum albumin and human gammaglobulin in different conjugation ratios failed to activate B cells, whether the hapten-protein conjugates were soluble or precipitated, whether the experiments were carried out in the presence or absence of different concentrations of sera from different species, and irrespective of the day of assay. Furthermore, the same FITC-protein conjugates or FITC itself coupled to Sepharose particles failed to induce a specific anti-FITC response, even though a range of 10-9-fold concentrations of FITC were used. In contrast, FITC coupled to lipopolysaccharide (LPS) regularly induced a primary anti-FITC response in all the above systems, whether FITC-LPS was soluble or coupled to Sepharose particles. The conjugation ratio of FITC to LPS was within the range of epitope densities used with FITC-protein conjugates. Analogous studies were performed with the above compounds and, in addition, NNP-cap and fowl gammaglobulin, added alone or together with LPS to lymphocyte cultures. In no case did the antigen plus LPS give a better specific anti-FITC response than LPS alone, irrespective of the culture conditions, the epitope densities, the physical form of the conjugates, and whether they were bound to Sepharose particles or not, although this would be expected in terms of the two-signal concept. The results are compatible with the one nonspecific signal hypothesis, ascribing a passive role to the Ig receptors and an active triggering function to thymus-independent antigens. Therefore, the ability to trigger B cells directly will depend on the nature of the carrier, triggering being achieved if the carrier is a polyclonal B-cell activator; the epitope density and the degree of cross-linking of Ig receptors are unimportant for delivering the triggering signal, although they can facilitate the binding of the conjugate to the specific B cells.

Animals↗
PubMed1975

Mechanism of B-cell activation and paralysis by thymus-independent antigens. Additive effects between NNP-LPS and LPS in the specific response to the hapten.

Normal spleen cells showed a bell-shaped dose response profile when stimulated in vitro with the thymus-independent antigen (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP)-lipopolysaccharide (LPS) with regard to the development of high-avidity plaque-forming cells to NNP. The addition of suboptimal concentrations of LPS to cultures stimulated by suboptimal concentrations of NNP-LPS resulted in optimal induction of B cells in that affinity fraction. Addition of LPS to cultures optimally stimulated by NNP-LPS resulted in paralysis of the specific cells. These results are interpreted in terms of the additive effects between the mitogenicity of LPS and the mitogenicity of NNP-LPS, the latter being selectively focused on the specific cells, thus providing further evidence for the 'one nonspecific signal' hypothesis for immune activation of B cells.

Adjuvants, Immunologic↗
PubMed1975

Effect of polyclonal B-cell activators on DNA synthesis in fibroblasts.

The polyclonal B-cell activators (PBA) lipopolysaccharide (LPS), type III pneumococcal polysaccharide (SIII), dextran, dextran sulphate, pentosan sulphate, and polyvinylpyrrolidone (PVP) were found to cause an increased DNA synthesis in mouse fibroblast monolayer cultures in the presence of calf serum, provided the background cpm were within certain values. The same PBA suppressed DNA synthesis when the cultures showed high background [corrected] cpm. Since the PBA did not activate DNA synthesis in serum-free cultures, it was concluded that PBA could be directly activate fibroblasts but rather influenced factors responsible for regulation of DNA synthesis in fibroblasts. In contrast PBA directly trigger lymphocytes.

Animals↗
PubMed1974

Effect of B-cell mitogens on lymphocyte subpopulations possesing C'3 and Fc receptors.

By the use of a rosette method allowing the detection at the cellular level of lymphocytes simultaneously binding Fc- and C'3-sensitized red cells it was found that about 70% of the rosette-forming cells from spleens of nude and normal mice possessed receptors for both Fc and C'3, whereas 30% only had Fc receptors. Very few, if any, lymphocytes possessed only C'3 receptors. The B-cell mitogens, purified-protein derivative of tuberculin (PPD), lipopolysaccharide from Escherichia coli (LPS), and pneumococcal polysaccharide type SIII (SIII), induced marked changes of these receptor-bearing lymphocytes. PPD caused a rapid loss of cells capable of binding C'3 and a concomitant increase of only Fc-binding cells, which was detected after only 24 h. LPS and SIII induced analogous changes, but they were not detected until 48 h and were not complete until after 72 h. It is suggested that immature lymphocytes possess both Fc and C'3 receptors and lose the latter receptor upon differentiation induced by B-cell mitogens PPD. and LPS would affect different populations of B cells, PPD-activating cells that have already reached a higher differentiation stage, whereas LPS and SIII would activate more immature B cells.

Animals↗
PubMed1974

Mechanism of thymus-independent immunocyte triggering. Mitogenic activation of B cells results in specific immune responses.

The present experiments were performed in order to analyze the mechanism by which thymus-independent antigens (nonspecific B-cell mitogens) can induce specific immune responses to antigenic determinants present on the same molecule. The hapten NNP was coupled to the B-cell mitogen, lipopolysaccharide (LPS). The conjugate retained full mitogenic activity and bound specifically to NNP-reactive cells. NNP-LPS activated polyclonal as well as specific anti-NNP antibody synthesis, but the optimal concentrations for induction of specific anti-NNP cells were several orders of magnitude lower than the concentrations required for polyclonal activation. These low concentrations failed to activate nonspecific cells, but they induced specific thymus-independent responses of high-avidity NNP-specific cells with the typical kinetics of antigenic responses in vitro. Furthermore, hapten-specific cells were paralyzed by NNP-LPS concentrations that were optimal for induction of polyclonal activation. Specific activation and paralysis could be abolished by free hapten indicating that selective binding of NNP-LPS to hapten-specific cells was responsible for the specificity of the response. However, the triggering signal lacked specificity, since high-avidity specific anti-NNP cells could still be activated by stimulating concentrations of NNP-LPS in the presence of free hapten, even though the Ig receptor combining sites were presumably occupied by NNP. The findings show that B cells with specific Ig receptors for the antigenic determinants on mitogen molecules preferentially bind these molecules and become activated at concentrations still unsufficient to trigger other B cells that lack specific receptors. It is suggested that activation for primary IgM responses in B cells is the result of "one nonspecific signal." This nonspecific signal is provided by the mitogenic properties of some antigens (highly thymus independent or, alternatively, by nonspecific T-cell factors (for highly T cell-dependent antigens), or both, and the surface structures responsible for triggering are not the Ig receptors. The specific Ig receptors only act as passive focusing devices for nonspecific stimuli, entitling the cell to be selectively activated, even though both the signal and the receptors for the triggering are nonspecific.

Animals↗