Control of B Cell Activation by Helper T Cells

Cell couples have been formed by mixing an antigen-and Ia-specific cloned helper T-cell line with a B-cell hybridoma presenting the antigen. By immunofluorescence observations, we have shown that the microtubule-organizing center (MTOC) inside the helper T cell, but not in the bound antigen-presenting cell, becomes oriented to face the area of specific cell-cell contact. This MTOC orientation is antigenand Ia-specific, and thus provides direct evidence for the specific interaction of a helper T cell with a B cell. It is presumed that the function served by this MTOC orientation, which is accompanied by the coordinate reorientation of the Golgi apparatus, is to target Golgi apparatus-derived secretory vesicles, containing putative lymphokines and/or growth factors, from the helper T cell directly to the antigen-presenting cell.One ofthe major roles ofT lymphocytes in immune responses is to regulate the activities ofother T cells, of B lymphocytes, and of macrophages. It has long been thought that T cells become activated and also directly signal other cells during specific cell-cell contact. This view of T-cell action gained widespread acceptance after it was discovered that T cells do not recognize antigen (Ag) in soluble form but only in conjunction with determinants of the major histocompatibility complex (MHC) found on cell surfaces (1-3). This so-called MHC restriction of T cells to allele-specific determinants of MHC ensures that T cells will be triggered only when they interact with cells bearing both appropriate MHC determinants and determinants of the Ag for which the T cell is specific. The interaction of cytotoxic T cells with potential targets has been demonstrated, and conjugates of T-cell effectors with targets can be isolated quite easily (4). However, the direct interaction of helper T cells with macrophage or B cells has been much more difficult to visualize. Several reports of T cells clustering with macrophages and B cells have been made over the last decade (5-7), but it has been difficult in these instances to establish definitively the specificity and/or the physiological relevance of the interactions. In the reports of Sweirkosz et al. (8) and Inaba et al. (7), there were indications that T cells that had been selected on macrophages bearing Ag were enriched for Ag-specific function, but these techniques are not sufficiently straightforward to have been used routinely. Although it is clear that B cells can present Ags to T cells in an MHC-restricted fashion (9, 10), and it has been shown that Ag-specific T-cell hybridomas bind to monolayers of Ag-pulsed B-cell lymphomas or hybridomas (11), there are no reports of the production and examination of specific cell couples between helper T cells and B cells. On the other hand, for many aspects of the T-cell regulation of antibody production to make sense, it is necessary to postulate direct interaction of T cells with B cells and to suggest that such an interaction first triggers the T cell to respond and that the T-cell response then e...

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“…However, under conditions of limiting Ag, strong preference. is observed in helping the Ia-specific Ag-presenting B cell (36).…”

Section: Discussionmentioning

confidence: 99%

The specific direct interaction of helper T cells and antigen-presenting B cells.

Kupfer¹,

Swain²,

Janeway³

et al. 1986

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

166

101

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“…Both types of response, however, critically depend upon activation of CD4' T cells. [1][2][3][4][5][6][7][8][9][10][11][12], the mediation of delayed-type hypersensitivity (DTH) responses [13-151, the cytolysis of major histocompatibility (MHC) class I1 antigen-bearing target cells "5-221, and in some cases the [I 71211 suppression of antibody secretion [23,24]. Further analyses of cloned CD4' T cells indicate that they can be separated into two distinct subsets with distinctions in their functional capabilities [7,12,251 and in the panel of cytokines released upon activation [26].…”

Section: Introductionmentioning

confidence: 99%

Differential activation of cytokine genes in normal CD4‐bearing T cells is stimulus dependent

et al. 1989

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Studies of cloned CD4+ T cell lines have shown that they can be separated into two distinct subsets with distinctions in their functional capabilities and by the differential release of either interleukin 2 (IL 2) (TH1/inflammatory type) or IL 4 (TH2/helper type) upon activation. To establish if in vivo-derived CD4+ T cells can exhibit distinct subsets we have investigated whether normal CD4+ T cells demonstrate differential expression of IL 2 and IL 4 mRNA, and secretion of IL 2 and IL 4 after primary stimulation in vitro. Utilizing the technique of in situ hybridization IL 2 and IL 4 gene expression in individual CD4+ T cells was readily detectable after concanavalin A (Con A) phytohemagglutinin (PHA) or pokeweed mitogen (PWM)-mediated activation. The frequencies of activated T cells producing IL 2 and IL 4 mRNA after Con A or PHA activation were approximately equivalent (30-40% of cells); however, after PWM activation the number of CD4+ T cells expressing IL 4 mRNA (78%) was more than twofold greater than the number of cells producing IL 2 mRNA (30%). Maximal levels of IL 2 gene expression occurred 24 h after mitogen activation whereas the highest levels of IL 4 mRNA were not detected until 48 h after mitogen activation. Similar distinctions in the kinetics of IL 2 and IL 4 secretion after mitogen activation were also found demonstrating good concordance in the observed expression of IL 2 and IL 4 mRNA and the levels of secreted lymphokines detected by bioassay. Most importantly, we have shown by in situ hybridization analysis that the majority of individual CD4+ T cells produce only IL 2 or IL 4 mRNA, and not both, after primary activation in vitro. By contrast, most CD4+ T cells activated in the presence of PMA and ionophore express both IL 2 and IL 4 mRNA. Our studies demonstrate that in normal, non-clonal populations of CD4+ T cells, the production of IL 2 and IL 4 is independently regulated in the majority of cells and appears to be stimulus dependent.

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“…To test this hypothesis, the expression of class II molecules from the four haplotypes H-2 b , H-2 d , H-2 k , and H-2 q was measured on fresh splenic macrophages, on activated macrophages represented by bone marrowderived macrophages (BMDMs), on fresh splenic B cells, and on lipopolysaccharide (LPS)-activated splenic B cells. The latter cell type, known to show relatively high expression (19) and not expected to release an IL-4 counter cytokine (20), served as a control. In addition, the cytokine responses of T cells restricted by protective, neutral, or disease-associated haplotypes were investigated.…”

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confidence: 99%

Differential expression of major histocompatibility complex class II genes on murine macrophages associated with T cell cytokine profile and protective/suppressive effects

Baumgart

Moos

Schuhbauer

et al. 1998

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

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Control of B Cell Activation by Helper T Cells

Cited by 11 publications

References 36 publications

The specific direct interaction of helper T cells and antigen-presenting B cells.

The specific direct interaction of helper T cells and antigen-presenting B cells.

Differential activation of cytokine genes in normal CD4‐bearing T cells is stimulus dependent

Differential expression of major histocompatibility complex class II genes on murine macrophages associated with T cell cytokine profile and protective/suppressive effects

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