The one signal theory of B cell activation revisited: A role for surface immunoglobulin in regulating T‐independent antibody responses?

Mamchak, Alusha A.; Hodgkin, Philip D.

doi:10.1038/icb.1995.43

Cited by 6 publications

(9 citation statements)

References 26 publications

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“…In the latter situation, it is still a matter of debate whether activation can be initiated solely by cross-linking of mitogen receptors or whether additional signals are required (60). Here, we show that a distinct CD44 variant isoform, namely CD44v10, is expressed on a subpopulation of BMC as well as on T-cell blasts, B-cell blasts and activated monocytes.…”

Section: Discussionmentioning

confidence: 81%

Involvement of CD44 exon v10 in B‐cell activation

1998

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The family of CD44 glycoproteins has been suggested to be involved in lymphocyte homing, maturation and activation. Using in vitro blocking studies with a monoclonal antibody, we here addressed the question of functional activity of CD44 variant exon v10 (CD44v10) in B-cell activation. We became interested in this question by the observation that CD44v10O was transiently expressed on activated T cells, B cells and monocytes as well as on a subpopulation of bone marrow cells. A potential ligand, as revealed by staining with a CD44v10 receptor globulin, was only detected on monocytes. Anti-CD44v10 had no major impact on T-cell activation and no influence on primed B cells, but interfered with the mounting of a primary B-cell response to T-independent and T-dependent antigens. Addition of anti-CD44v10 at different stages during the activation process revealed that CD44v10 was not engaged in B-cell-T-cell interactions. The antibody exerted some effect on monocyte activation as defined by a slight decrease in IL-1 production, but most efficiently inhibited antigen-specific as well as mitogen-induced B-cell activation when present during the coculture of virgin B cells with monocytes. These findings, together with the observation that a CD44v10 ligand was only detected on monocytes but not on lymphocytes, point towards a requirement for CD44v10 in a B-cell-monocyte interaction. Furthermore, since activation of B cells by engagement both of the B-cell receptor and of mitogen receptors was inhibited by anti-CD44v10, the data suggest that a costimulatory function of CD44v10 proceeds independent of the B-cell receptor.

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Section: Discussionmentioning

confidence: 81%

Involvement of CD44 exon v10 in B‐cell activation

1998

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“…Media depletion would not account for this downturn, because it occurred at much lower overall LPS concentrations. We have previously suggested that a sIg‐mediated (antigen) signal could be responsible by inhibiting LPS‐induced antigen‐specific ASC formation 27 . This hypothesis predicts that the cross‐linking of sIg by a hapten coupled to a non‐mitogenic carrier would induce a signal that could inhibit LPS‐induced antigen‐specific ASC formation.…”

Section: Resultsmentioning

confidence: 99%

“…It is now clear that sIg can mediate transmembrane and intracellular signals (reviewed by Cambier and Campbell, 14 Campbell et al , 15 Reth 16 and DeFranco 17 ) and that these signals play subtle and variable roles in the regulation of B cell behaviour that are dependent on the type of B cell activator and the differentiation state of the cell 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 . Previously, we proposed a hypothesis to reconcile Coutinho and Möller's one‐signal model with sIg‐ mediated signalling 27 . This hypothesis suggested that the antigen signal may have played a role in the generation of Coutinho and Möller's 2 , 4 bell‐shaped dose–response curves for LPS‐induced antigen‐specific ASC formation 27 .…”

Section: Introductionmentioning

confidence: 97%

“…Previously, we proposed a hypothesis to reconcile Coutinho and Möller's one‐signal model with sIg‐ mediated signalling 27 . This hypothesis suggested that the antigen signal may have played a role in the generation of Coutinho and Möller's 2 , 4 bell‐shaped dose–response curves for LPS‐induced antigen‐specific ASC formation 27 . In the present paper, we experimentally re‐examine two important assumptions of Coutinho and Möller's one signal theory: 4 (i) the inhibitory nature of high doses of LPS; and (ii) the lack of any role for sIg‐mediated signalling in the antihapten response.…”

Section: Introductionmentioning

confidence: 99%

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Absence of lipopolysaccharide high‐dose paralysis in B‐cell responses: Implications for the one‐signal theory

Mamchak

Hodgkin

2000

Immunol Cell Biol

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IntroductionLipolysaccharide (LPS), a component of the cell wall of gram-negative bacteria, is able to induce B cell activation resulting in proliferation and Ig production.1,2 Recently, Tolllike receptor 4 (Tlr4) has been implicated in the signalling pathway that leads to LPS-induced activation.3 However, how Tlr4 or other cellular components interact with LPS and induce cellular changes associated with differentiation is still poorly understood. Despite this lack of mechanistic information, a comprehensive picture of the dynamics and doseresponse features of LPS stimulation was reported by Coutinho and Möller in a series of classic studies (reviewed by Coutinho and Möller 4 ). A feature of these experiments was the observation of two bell-shaped dose-response curves. In the first, the generation of antibody secreting cells (ASC) increased with LPS concentration to reach an optimum and then reduced as the concentration was increased further. The second bell curve occurred when haptenated LPS was used as the stimulus and the production of antihapten specific cells was measured. Here, the bell curve appeared at substantially lower overall LPS concentrations than for the first example. These authors argued that the two bell curves were analagous, with high LPS concentrations inhibiting the development of ASC by a form of cellular paralysis. The reason for the shift in sensitivity for the antigen-specific cells, they reasoned, was that surface immunoglobulin (sIg) played a passive (non-signalling) role in B cell activation by focusing LPS to the surface of the hapten-specific B cells, thereby promoting antigen-specific responses at much lower total LPS concentrations. 2,5,6 Although Coutinho and Möller's experiments were based on the mode of action of a highly potent B cell mitogen, they generalized their concept to include T-dependent B cell activation in their 'one-signal theory' of B cell activation. By this view, the antigen receptor on the B cell, once bound to antigen, serves to attract an appropriate T cell to deliver a potent activating signal, which does not require a signal from the B cell receptor itself. This latter prediction 4 has been borne out by experiments that revealed that, in the absence of an antigen (sIg-mediated) signal, activated T cell membranes or the interaction between CD40 and its ligand are sufficient to stimulate B cell proliferation and, in combination with Th2 cytokines, antibody secretion. Summary Over 20 years ago, Coutinho and Möller reported that high concentrations of LPS were paralytic for the development of antibody secreting cells (ASC). This data was used to explain bell-shaped dose-response curves observed for antihapten antibody formation in response to haptenated LPS. In turn, this bell curve was used to formulate the one-signal model of B cell activation, which argued that antigen signalling was generally unimportant to B cell responses. The present paper re-examines LPS dose-response curves and finds results that do not support the view that high doses of LPS inhibit ...

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“…Low-dose, low-affinity stimulation does not inhibit ASC differentiation but also has little effect on isotype switching. Thus, most Ab produced following these activation conditions will be low-affinity IgM Ab, as previously postulated (47,48). Although we remain unsure of the physiological relevance of these observations, it is possible that isotype-switched, high-affinity B cells are preferentially directed to a memory pool rather than to plasma cell differentiation.…”

Section: Discussionmentioning

confidence: 84%

High-Affinity B Cell Receptor Ligation by Cognate Antigen Induces Cytokine-Independent Isotype Switching

Turner

Corcoran

Brink

et al. 2010

The Journal of Immunology

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The selection of an appropriate Ig isotype is critical for an effective immune response against pathogens. Isotype regulation is sensitive to external signals, particularly cytokines secreted by Th cells. For example, IL-4 induces isotype switching to IgG1 via a STAT6-dependent signaling pathway. In this study, we show that BCR ligation also induces IgG1 switching in mouse B cells. The extent of switch induction by Ag is affinity-dependent, and high-affinity Ag binding leads to IgG1 switching levels comparable to those induced by saturating IL-4. However, the Ag-induced IgG1 switch does not require additional cytokine signals and occurs in a STAT6-independent manner. Thus, BCR ligation represents a novel pathway for direct isotype switching leading to IgG1 secretion.

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The one signal theory of B cell activation revisited: A role for surface immunoglobulin in regulating T‐independent antibody responses?

Cited by 6 publications

References 26 publications

Involvement of CD44 exon v10 in B‐cell activation

Involvement of CD44 exon v10 in B‐cell activation

Absence of lipopolysaccharide high‐dose paralysis in B‐cell responses: Implications for the one‐signal theory

High-Affinity B Cell Receptor Ligation by Cognate Antigen Induces Cytokine-Independent Isotype Switching

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