The Role of CD40–CD40 Ligand Interactions in Suppression of Human B Cell Responsiveness by CD4+ T Cells

Hirohata, Shunsei

doi:10.1006/cimm.1997.1209

Cited by 4 publications

(6 citation statements)

References 46 publications

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“…In fact, IL-12 enhanced the capacity of immobilized anti-CD3 activated CD4 T cells to stimulate resting B cells to express CD25, whereas IL-10 decreased it (data not shown). By contrast, compared with CD4 T cells activated with immobilized anti-CD3 alone, CD4 T cells activated with immobilized anti-CD3 and IL-12 displayed stronger suppression of immunoglobulin production by B cells activated with immobilized anti-CD3 stimulated mitomycin C-treated CD4 T cells [8] (data not shown). These results indicate that the changes of CD40L expression on anti-CD3 stimulated CD4 T cells driven by IL-12 or IL-10 parallel their capacity to activate resting B cells and to suppress previously activated B cells.…”

Section: B Cells Do Not Abrogate the Enhancing Effects Of Il-12 On Thmentioning

confidence: 88%

“…A number of studies have disclosed that CD40± CD40L interactions play a critical role in T cell-dependent B cell activation, proliferation, and differentiation [4±6]. Moreover, it has recently been shown that during T cell±B cell collaboration, CD40±CD40L interactions exert bidirectional effects on B cell immunoglobulin production, depending on the state of activation of B cells and on the extent of CD40 ligation [7,8]. Thus, the regulation of the expression of CD40L on CD4 T cells is crucial for the outcome of humoral immune responses.…”

Section: Introductionmentioning

confidence: 99%

“…In fact, the current study has shown that the changes of CD40L expression on anti-CD3 stimulated CD4 T cells driven by IL-12 or IL-10 parallel their capacity to activate resting B cells to express CD25. Of interest, recent studies have indicated that CD40±CD40L interactions exert bidirectional effects in the B cell responses depending on the state of activation of B cells and on the extent of CD40 ligation [7,8].…”

mentioning

confidence: 99%

“…Thus, higher saturation of CD40 with CD40L inhibits the growth and immunoglobulin secretion of human B cell hybridomas [31] as well as those of peripheral blood B cells activated by anti-CD3 stimulated CD4 T cells [7,8]. In fact, IL-12 enhanced the capacity of CD4 T cells activated with immobilized anti-CD3 to suppress immunoglobulin production by activated B cells.…”

mentioning

confidence: 99%

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Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand

Hirohata

1999

Clinical and Experimental Immunology

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SUMMARYIL-12 is the prominent inducer of Th1 responses in humans and in the mouse. CD40 ligand (CD40L) plays important roles in regulation of immune responses, including T cell-dependent activation of B cells and cytokine production by monocytes and dendritic cells. The present study examined the in¯uences of IL-12 on the CD40L expression of activated human CD4T cells. IL-12 enhanced CD40L expression on CD4T cells stimulated with immobilized anti-CD3 in the complete absence of accessory cells, whereas IL-4 and IL-10 decreased it. Exogenous interferon-gamma (IFN-g) did not increase CD40L expression on immobilized anti-CD3 stimulated CD4T cells at any time up to 168 h of culture. The IL-12-induced enhancement of CD40L expression on anti-CD3 activated CD4T cells was not in¯uenced in the presence of a metalloproteinase inhibitor KB8301, which up-regulated CD40L expression by preventing the processing of membrane-bound CD40L, or B cells, which down-regulated CD40L expression by receptor-mediated endocytosis. These results indicate that IL-12 enhances the CD40L expression of activated CD4T cells independently of the IFN-g production. The data thus suggest that Th1 responses induced by IL-12 might play an important role in the regulation of humoral immune responses through up-regulated CD40L expression.

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Section: B Cells Do Not Abrogate the Enhancing Effects Of Il-12 On Thmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand

Hirohata

1999

Clinical and Experimental Immunology

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“…After BCR signaling, mainly in the periphery, immature IgM ϩ B cells follow one of three fates: receptor editing (19,20), clonal deletion (21), or clonal anergy (22). Although CD40 appears to participate in B cell clonal anergy (23,24), its possible role in other forms of B cell tolerance has not been clarified.…”

mentioning

confidence: 99%

Does CD40 Ligation Induce B Cell Negative Selection?

Martínez-Barnetche

Madrid‐Marina

Flavell

et al. 2002

The Journal of Immunology

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Binding of CD154 to its receptor, CD40, provides costimulation for mature B cell activation and differentiation in response to Ag receptor signals. In mice, early B cell precursors express CD40, but its function at this stage is unknown. We examined the effects of CD40 ligation during B cell ontogeny in transgenic mice constitutively expressing CD154 on B cells (κEP-CD154). Precursors beyond pro-B cells were absent in adult bone marrow but were increased in the fetal liver. Newborn κEP-CD154 mice had largely increased numbers of peripheral B cells, which were CD154+, and that 36 h after birth expressed high surface levels of CD23 and MHC class II, resembling activated mature B cells. Nevertheless, κEP-CD154 mice were hypogammaglobulinemic, indicating that the expanded population of apparently activated B cells was nonfunctional. Further analysis revealed that soon after birth, κEP-CD154 mice-derived B cells became CD5+/Fas+, after which progressively decreased in the periphery in a CD154-CD40-dependent manner. These results indicate that CD40 ligation during B cell ontogeny induces negative selection characterized by either hyporesponsiveness or an arrest in maturation depending on the time of analysis and the anatomic site studied.

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Enhanced Production of IgE Anti-Japanese Cedar Pollen Specific Antibodies by Peripheral Blood B Cells from Patients with Japanese Cedar Pollinosis

Ohshima

Hirohata

2008

Allergology International

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The Role of CD40–CD40 Ligand Interactions in Suppression of Human B Cell Responsiveness by CD4+ T Cells

Cited by 4 publications

References 46 publications

Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand

Human Th1 responses driven by IL-12 are associated with enhanced expression of CD40 ligand

Does CD40 Ligation Induce B Cell Negative Selection?

Enhanced Production of IgE Anti-Japanese Cedar Pollen Specific Antibodies by Peripheral Blood B Cells from Patients with Japanese Cedar Pollinosis

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