Molecular Basis of B‐Cell Activation

Coutinho, António; Möller, Göran; Richter, Wolfgang

doi:10.1111/j.1365-3083.1974.tb01263.x

Cited by 98 publications

(20 citation statements)

References 30 publications

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“…It is clear from the present results that T helper cells can discriminate perfectly well between TNP, FITC and SP when they are coupled to syngeneic cells. Both of these conclusions support the notion that antigen recognition per se is of no functional consequence for B cells [29] and extend its experimental demonstration to B lymphocytes activated by a cooperative process.…”

Section: Discussionsupporting

confidence: 56%

Hapten‐specific helper T cells. I. Collaboration with B cells to which the hapten has been directly coupled

Martínez-Alonso

Coutinho

Bernabé³

et al. 1980

Eur J Immunol

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A new system to obtain large numbers of functionally competent hapten-specific effector helper T cells has been developed. Mice were primed in the tail with syngeneic spleen cells derivatized with one of three different haptens: 2,4,6-trinitrophenyl, fluorescein isothiocyanate and 3-(p-sulfophenyldiazo)-4-hydroxyphenyl. Draining lymph node cells were subsequently restimulated in culture with the homologous antigen for periods up to 6 weeks. More than 99% and 90% of the cells recovered from these preparative cultures, expressed Thy-1 and Lyt-1 antigens, respectively. These cells proliferated specifically in response to the homologous stimulation by haptenated syngeneic spleen cells, and they were found to display very high levels of hapten-specific helper activity, as assayed in a new, universal method for testing T -B cell cooperation, where every B cell can potentially respond to specific T cell help. Coculture of hapten-derivatized, functionally competent B cells with hapten-specific T cells obtained from the preparative cultures, resulted in the appearance, and exponential increase with time, of very large numbers of IgM and IgG plaque-forming cells. This helper activity could be shown to be: specific for the immunizing hapten and to increase with the time of in vitro helper cell enrichment, which also resulted in higher average avidities expressed by the helper cell populations. This methodology appears valuable for structural studies on hapten-specific helper cells, as well as for the functional analysis of effector helper -B cell interactions.

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Section: Discussionsupporting

confidence: 56%

Hapten‐specific helper T cells. I. Collaboration with B cells to which the hapten has been directly coupled

Martínez-Alonso

Coutinho

Bernabé³

et al. 1980

Eur J Immunol

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“…B cell unresponsiveness is commonly defined by the failure of mounting an antibody response upon a n antigenic challenge. However, it is well known that many mechanisms can operate at the level of the immune system in general, resulting in a failure of the animal t o produce specific antibodies, without involving a true state of B cell tolerance [5,61. In many cases, the animal or the system is unresponsive, whereas the B cells are resting lymphocytes, perfectly competent to be activated.…”

Section: Introductionmentioning

confidence: 99%

“…Actually, self-reacting B cells are k n o w n t o exist in normal conditions [4 1, 421 and, as discussed before [5], this poses n o special problems if selfdeterminants are, as they should b e expected t o be, thymusdependent. Self-nonself discrimination, therefore, has to b e clearly defined only at t h e T cell level.…”

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confidence: 99%

Hapten‐induced B cell paralysis. II. Evidence for trivial mechanisms of tolerance

Gronowicz

Coutinho

1975

Eur J Immunol

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Injection into mice of a free reactive form of the hapten (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP), induces a state of specific unresponsiveness to the hapten, upon its challenge with thymus-cependent and independent carriers. This unresponsiveness is maintained in vitro. Both induction and expression of the unresponsive state were found to be independent of T cells. Analysis of the mechanisms responsible for the B cell "tolerance" demonstrated that the major cause of unresponsiveness in this system is the blockade of specific surface receptors on B cells by the hapten, abolishing the focusing function of these receptors. "Tolerant" B cells, though they were unresponsive to the antigen, could be activated to anti-hapten antibody secretion by the B cell mitogen lipopolysaccharide (LPS), which does not require Ig-mediated binding. They also became fully responsive to the antigen NNP-LPS in specific thymus-independent responses after 24 hours of in vitro incubation in the absence of tolerogen, conditions which allow "deblocking" of Ig surface receptors, and, thus, restoration of the focusing function of these receptors. These results demonstrate that great care is required for a clearcut definition of B cell tolerance. In this example, the tolerant B cells were perfectly responsive to a competent ligand, and no indication of an altered triggering or effector processes was found. It appears that in this, as in many other cases of B cell tolerance, the systems or the animals are tolerant, whereas B cells maintain a resting nonactivated state and are fully responsive to the triggering signal. Thus, the existence of tolerance-inducing signals resulting in B cell unresponsiveness is questioned.

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“…Whether the function of the sIg molecule is to passively focus T-cell help onto the B-cell membrane (1) or whether the binding of antigen to sIg also fulfills a signalling function (2) has been a matter of contention. Resolution of this controversy requires that the Th-cell and Bcell specificities for antigen be dissociated, and T-cell specificity must be selected such that efficient T-B interaction occurs independently of the involvement of sIg.…”

mentioning

confidence: 99%

Role of cell surface immunoglobulin in B-lymphocyte activation.

Locascio¹,

Haughton²,

Arnold³

et al. 1984

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

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The role of cell surface immunoglobulin in helper T-cell-dependent B-cell activation was analyzed using a B-cell lymphoma, CH12, with known antigen specificity and activation properties similar to those of a resting B cell. Two sources of helper T cells were used, both selected such that they interact with H-2-encoded determinants on CH12 in the absence of the specific B-cell antigen, sheep erythrocytes. By this dissociation of the specificity of the T cells from that of the B cells, the requirement for antigen in the induction of CH12 to antibody secretion could be studied. The results show that both helper T-cell-B-cell interactions and surface immunoglobulin-antigen binding are involved in inducing B-cell differentiation, thus establishing a signalling function for the antigen receptor on B lymphocytes. Our data also show that the requirement for surface immunoglobulin-ligand interactions in B-cell activation can, under certain conditions, be circumvented, notably when high (nonphysiologic) multiplicities of Tcell help are used.The binding of antigen to surface immunoglobulin (sIg) on the B-cell membrane facilitates the interaction of antigenspecific helper T (Th) cells with specific B cells by "bridging" the two cell types. Whether the function of the sIg molecule is to passively focus T-cell help onto the B-cell membrane (1) or whether the binding of antigen to sIg also fulfills a signalling function (2) has been a matter of contention. Resolution of this controversy requires that the Th-cell and Bcell specificities for antigen be dissociated, and T-cell specificity must be selected such that efficient T-B interaction occurs independently of the involvement of sIg. Such a method is suggested by the work of Augustin and Coutinho (3) MATERIALS AND METHODS Animals. B10.H-2aH-4bp/Wts (2a4b) mice were bred and maintained under pathogen-free conditions at the University of North Carolina. (BALB/c x C57BL/6)F1 (CB6F1, H2d/b), BALB/c (C, H-2d), and C3H/HeJ (C3H, H-2) mice were purchased from The Jackson Laboratory and maintained in the animal colony at Duke University. All mice were 8-to 12-wk old when used. CH12 Lymphoma Cells. CH12 arose in a 2a4b mouse and was propagated as an ascites tumor. The induction, characterization, and identification of the tumor cells' specificity for SRBC have been described (10). From the ascites, 94.3 + 5.5% of the cells were ,u by immunofluorescence (10 experiments) while 1.2 ± 0.4% were nonspecific esterase positive (four determinations). The role, if any, that these latter cells in the tumor preparation might play in the activation of CH12 has not been analyzed. In 8 experiments, 89.9 ± 6.4% of the cells rosetted with SRBC but none with human erythrocytes or mouse erythrocytes (MRBC). We have recently found that this apparent specificity for SRBC is likely to be a cross-reaction with autologous effete erythrocytes, because CH12 rosettes as efficiently with bromelain-treated MRBC (12) as with SRBC. Greater than 95% of cells are positive for the CH12 idiotype, as determined...

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Molecular Basis of B‐Cell Activation

Cited by 98 publications

References 30 publications

Hapten‐specific helper T cells. I. Collaboration with B cells to which the hapten has been directly coupled

Hapten‐specific helper T cells. I. Collaboration with B cells to which the hapten has been directly coupled

Hapten‐induced B cell paralysis. II. Evidence for trivial mechanisms of tolerance

Role of cell surface immunoglobulin in B-lymphocyte activation.

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