One Non‐Specific Signal Triggers B Lymphocytes

Möller, G

doi:10.1111/j.1600-065x.1975.tb00154.x

Cited by 44 publications

(45 citation statements)

References 27 publications

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“…The existence of autoreactive cells was predicted from the "one nonspecific signal" hypothesis (5) and was confirmed by direct experiments (references 6 and 7, and footnote 2).…”

mentioning

confidence: 55%

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

Primi¹,

Hammarström²,

Smith³

et al. 1977

The Journal of Experimental Medicine

110

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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.

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“…The existence of autoreactive cells was predicted from the "one nonspecific signal" hypothesis (5) and was confirmed by direct experiments (references 6 and 7, and footnote 2).…”

mentioning

confidence: 55%

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

Primi¹,

Hammarström²,

Smith³

et al. 1977

The Journal of Experimental Medicine

110

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“…This implies a competition for surface receptors. fitted theoretBecause both polymer preparations have almost identical "ept between exitope densities" with a common carrier chemistry, this finding with cultured is in disagreement with theories that explain immunogenicity it was for the by invoking epitope density (2) or polyclonal (i.e., nonspecific) )oth cases, the activation by the "carrier" (24,25). than that preIn interpreting the above data, we wish to postulate several apten binding points concerning the nature of a specific T cell-independent stimulus: (i) a specific immunogenic signal is generated by the ;ponse in vitro formation of immunons on the surface of a responsive cell, (ii) polymer are an immunon will form only after a sufficient number of surface he data but is receptors are clustered, and (iii) specific clustering of surface receptors occurs as a consequence oftheir being bound to linked haptens.…”

Section: Hown In Figsmentioning

confidence: 84%

Specific cellular stimulation in the primary immune response: experimental test of a quantized model.

Dintzis¹,

Vogelstein²,

Dintzis³

1982

Proc. Natl. Acad. Sci. U.S.A.

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Dose-response and dose-suppression curves have been measured for the primary immune response in mice, in vivo and in vitro, by using size-fractionated linear polymers of acrylamide substituted with hapten. The results are in general agreement with a simple theory based on the premise that the specific primary immunological response is quantized at some fundamental and limiting step, requiring a minimum number of linked antigen receptors for response.The immune response to most antigens is a very complex phenomenon that has resisted quantitative analysis. Some of this complexity may be related to the molecular complexity of many of the antigens (e.g., proteins, cell walls, etc.) which have been used. A relatively simple and specific primary immune response occurs against antigens that are linear polymers of only a few types ofchemical subunits (1-3). These antigens give rise to a rapid primary immune response with the production ofspecific antibody molecules predominantly of the class IgM (4, 5). The immune response to these antigens may be relatively simple because of its rapidity and the apparent minimum involvement of thymus-derived lymphocytes (T cells). Although complex interactions involving suppressor cells, helper cells, and idiotypes seem to be important in more mature, T cell-dependent responses, it is likely, as discussed here, that they are not a dominant factor in the very early and rapid T cell-independent responses.It long has been observed that multivalent antigens are better immunogens than are monovalent ones; indeed, a number of investigators have proposed that triggering of immunocompetent cells (B cells) to form antibody requires adequate crosslinking of surface receptors by multivalent ligands (6)(7)(8)(9)(10)(11)(12)(13)(14). We have carried this important observation one step further by proposing that there is a specific number ofreceptors that must be linked together in order to deliver the triggering signal (15). The interaction site between antigen and receptor often has been proposed as occurring on the surface of B lymphocytes (16). Various kinds of antigen-presenting cells also may play a role at this site (17, 18); however, for the sake of simplicity, we have taken the limiting step to be one occurring on the external surfaces of B cells. We have described the preparation of and the in vivo immunological response to a series ofsize-fractionated linear polymers of acrylamide partially substituted with dinitrophenyl (Dnp) hapten (15), which behaved as "T cell-independent" antigens. Analysis of the responses elicited by a series of such polymer preparations led us to the conclusion that the primary immunological response at some basic and limiting level is quantized-i. e., a minimum specific number of antigen receptors (which we estimated to be -12-16) must be connected together as a spatially compact cluster, an "immunon," before an immunogenic signal is delivered to the receptor cell.The present paper gives the results ofusing size-fractionated Dnp-polyacrylamide preparation...

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“…An alternative to the two-signal mechanism has recently been proposed by Coutinho and M511er (33,34), who suggest that the only signal required to activate B cells is a single mitogenic stimulus provided either by activated T cells or by the antigen itself, in the case of thymus-dependent and thymusindependent antigens, respectively. Mitogenic stimulation by LPS, however, appears not to be sufficient to elicit an HGG response.…”

Section: Discussionmentioning

confidence: 99%

Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS.

Skidmore¹,

Chiller²,

Weigle³

et al. 1976

The Journal of Experimental Medicine

131

124

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Bacterial lipopolysaccharide (LPS) I has among its broad spectrum of immunologic activities the capacity to modulate the induction of a specific state of tolerance in mice to the thymus-dependent antigen human IgG (HGG), into a specific state of immunity to HGG (1). Mice treated with LPS shortly after the injection of a tolerogenic dose of deaggregated HGG (DHGG) not only fail to become tolerant to HGG (2), but demonstrate a delayed primary response to HGG, and also respond anamnestically to a subsequent immunogenic challenge of aggregated HGG (AHGG) (1). This phenomenon, which has been viewed as a very stringent test of an adjuvant effect (3), was originally described by Claman (4) with bovine gamma globulin tolerance in mice, and has also been seen more recently by Ornellas et al. (5) with sheep gamma globulin tolerance in rats.Recent studies have been directed toward precisely defining the cellular basis of this modulatory effect of LPS on HGG tolerance. It was found that the ' immune response to HGG which is seen as the result of dual treatment of mice with DHGG and LPS appears to occur in spite of the normal induction of tolerance in both HGG-specific thymocytes (1) and peripheral T cells (6). These observations suggest that LPS not only prevents tolerance induction in B cells, but also overcomes the normal requirement for HGG-specific T-helper cells. Furthermore, a positive correlation exists between the capacity of LPS to * This is Publication no.

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One Non‐Specific Signal Triggers B Lymphocytes

Cited by 44 publications

References 27 publications

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

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

Specific cellular stimulation in the primary immune response: experimental test of a quantized model.

Immunologic properties of bacterial lipopolysaccharide (LPS). III. Genetic linkage between the in vitro mitogenic and in vivo adjuvant properties of LPS.

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