Role of membrane receptors in the induction of an <i>in vitro</i> secondary anti‐hapten response I. Differentiation of B memory cells to plasma cells is independent of antigen‐immunoglobulin receptor interaction

Cammisuli, Salvatore; Henry, Claudia; Wofsy, Leon

doi:10.1002/eji.1830080910

Cited by 32 publications

(22 citation statements)

References 22 publications

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“…The assumption appears reasonable because the frequencies of LPS-induced PFC are in fact identical to the frequencies of LPS-reactive B cells of the same specificities, when determined in limiting-dilution conditions (7). These observations confirm previous reports that T cell-dependent B-cell activation could take place in the absence of specific interactions with Ig receptors of the responding cells (18), when memory cells were used, and they establish that this is also the case for normal, unprimed B cells.…”

Section: Polyclonality Of the T Cell-dependent B-cell Response The Msupporting

confidence: 91%

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Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function.

Augustin¹,

Coutinho²

1980

The Journal of Experimental Medicine

120

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The analysis of B-cell triggering mechanisms and clonal regulation has been successfully approached with ligands that are competent to activate a large fraction of all cells (1-3). Polyclonal activation of B cells has also proved to be a useful tool in studying Ig synthesis and secretion (4), in the analysis of functional B-cell subpopulations (5) and their development (6), and in the description of the antibody repertoire (7,8) by allowing the determination of relative frequencies of clonotypes in the absence of antigen selection.Each B-cell mitogen known to date activates only a fraction of all bone marrowderived lymphocytes (9, 10). Although some discrepancies in quantitative aspects of the problem still exist, it is now clear that partially distinct subsets of B cells respond to the various mitogens (5,11,12). In particular, much attention has been focused on the existence of B-cell subpopulations responding to either thymus-independent or thymus-dependent forms of the same antigenic determinants (13-16). As was pointed out before (10), this cell population that secretes antibodies subsequently to T cellmacrophage help has thus far escaped all analyses using direct B-cell mitogens. The study of this cell subset would provide new information on both its antibody repertoire and the mechanism of cooperative B-cell triggering which, to date, remains controversial (17).We attempted to develop a system for polyclonal B-cell induction mediated by T cells, in the absence of extraneously added ligands, such as antigen or mitogen. Previous experiments by Cammisuli et al. (18) had already indicated that cooperative B-cell induction could take place in the absence of specific interactions involving Ig receptors on the responding B cell, by using helper cell recognition of determinants artificially attached to B-cell surfaces. We have now improved that approach with three major modifications. To ensure that the antigens would remain on the B-cell surface throughout the cooperative culture, we activated T cells directly against minor antigens expressed on B-cell surfaces. Furthermore, we used an in vitro system by which a manifold enrichment of specific helper cells can be achieved. Finally, we measured the responses of all B cells, regardless of their antibody specificity. In this way, a very high frequency of specific T-B cell interactions was obtained in the helper assay, and this might make the system an optimal tool for the study of T-B cell collaboration.

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Section: Polyclonality Of the T Cell-dependent B-cell Response The Msupporting

confidence: 91%

“…Some, however, dealt with T-cell recognition of Ig idiotypes on responding B cells and are, therefore, equivalent to oligoclonal, antigen-dependent cooperation (35,36). Others, although bypassing Bcell Ig receptors, did not use enriched T cells and studied only the responses of antigen-specific B cells (18).…”

Section: Discussionmentioning

confidence: 99%

Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function.

Augustin¹,

Coutinho²

1980

The Journal of Experimental Medicine

120

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“…As an assay system we chose the activation of B cells to plaque-forming cells (PFC) by I-A compatible THy in the presence of the specific antigen. This model system was first described by Cammisuli et al [9], using a hapten-antibody sandwich technique to bridge T and B cells, and has since been employed by many investigators [lo-121, In our case, the THy would bind to the B cell because they would recognize antigen presented by la molecules on the B cell surface. Surprisingly, only the A chain-reactive THy were able to induce polyclonal B cell activation in the presence of beef insulin.…”

Section: Introductionmentioning

confidence: 94%

B cell activation potential of insulin‐reactive T cells in H‐2^b mice

Huber¹,

Hochman²

1984

Eur J Immunol

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The murine T cell response to heterologous insulins provides a good model system for studying the mechanism of immune response (Ir)-gene function, since insulin is a small, chemically well-defined molecule. H-2b mice respond predominantly to A chain loop determinants of beef insulin, presented by the I-A epitope Ia. W39. However, using a library of insulin-specific T cell hybridomas (THy), we previously found that immunization of H-2b mice with beef insulin activates a much wider population of T cells than are detected in T cell proliferation assays. Using such cloned THy we were able to study Ir-gene control at the level of antigen presentation. We compared the ability of the various THy to induce differentiation in I-A-matched B cells in response to antigen. Although both A and B chain-reactive clones respond with interleukin 2 production, they differ markedly in their potential to activate B cells in that only the former are able to induce B cell differentiation in the presence of the intact beef insulin molecule. The latter, however, can serve as helper cells in the presence of isolated B chain, and can synergize with a suboptimal concentration of A chain-reactive THy to induce an optimal B cell response. These results suggest that the insulin molecule is presented by I-Ab antigen-presenting cells in a very specific configuration that allows more effective T cell recognition of the A chain loop than the B chain determinants. To explain the discrepancy between the interleukin 2 assay and the induction of polyclonal activation, it can be assumed that in the former assay antigen is presented by macrophages, while presentation by B cells is necessary for induction of polyclonal activation. Macrophages are able to process the intact beef insulin molecule and, therefore, present B chain determinants, while nonimmune B cells may be unable to process antigen and could present B chain determinants only when the isolated B chain is given as antigen.

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“…One avenue of B cell triggering which is not considered in Figure !, is the activation of B cells via direct ("cognate") interactions with T cells. Several groups have observed that activated T cells are capable of triggering most, if not all, resting B lymphocytes to proliferation and Ig secretion without the requirement for the cross-linkage ofthe B cell's membrane Ig (Cammisuli et al 1978, Marrack & Kappler 1980, Augustin & Coutinho 1980, Tse et al 1981, Martinez-Alonso & Coutinho 1981, Jones & Janeway 1981. This finding has rekindled doubts about the role of Ig molecules as true receptors involved in B cell activation and has fortified earlier models proposing that membrane-bound Ig serves only to focus T cell signals (i.e., the true activation signals) onto resting B cells (Coutinho & Moller 1974).…”

Section: T Cell Triggering Of B Cellsmentioning

confidence: 99%

“…However, it does not appear that one can explain those instances of cognate help in which receptor cross-linkage does not occur simply by the local production of BMF. There is considerable evidence that substantial B cell proliferation occurs in instances in which T cells help B cell responses by recognizing B cell membrane antigens (Augustin & Continho 1980), or by recognizing exogeneous antigens bound non-specifically to B cell membranes (Cammisuli et al 1978, Marrack & Kappler 1980, Tse et al 1981, Jones & Janeway 1980). Recently, DeFranco etal.…”

Section: T Cell Triggering Of B Cellsmentioning

confidence: 99%

B Cell Growth and Differentiation Factors

Howard¹,

Nakanishi²,

Paul³

1984

Immunological Reviews

102

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The role of T lymphocytes in regulation of B cell responsiveness has been recognized for over a decade. Early studies assigned part of this regulation to a soluble product, initially designated T cell-replacing factor or TRF. Recently, investigators have discovered a level of factor complexity skillfully camouflaged by this simple term. Accordingly, the concept has now matured to encompass a battery of antigen non-specific, genetically unrestricted soluble factors which govern all aspects of B cell immunity: activation, proliferation, and differentiation. Here, we review our developing knowledge of this area. While many questions remain unresolved, there seems cause for optimism and a hope that increased understanding of these factors and their mode of action will eventually reveal the basis of B cell immunoregulation.

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Role of membrane receptors in the induction of an in vitro secondary anti‐hapten response I. Differentiation of B memory cells to plasma cells is independent of antigen‐immunoglobulin receptor interaction

Cited by 32 publications

References 22 publications

Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function.

Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function.

B cell activation potential of insulin‐reactive T cells in H‐2^b mice

B Cell Growth and Differentiation Factors

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Role of membrane receptors in the induction of an in vitro secondary anti‐hapten response I. Differentiation of B memory cells to plasma cells is independent of antigen‐immunoglobulin receptor interaction

Cited by 32 publications

References 22 publications

Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function.

Specific T helper cells that activate B cells polyclonally. In vitro enrichment and cooperative function.

B cell activation potential of insulin‐reactive T cells in H‐2b mice

B Cell Growth and Differentiation Factors

Contact Info

Product

Resources

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B cell activation potential of insulin‐reactive T cells in H‐2^b mice