Regulation of cytoplasmic, surface and soluble forms of CD40 ligand in mouse B cells

Wykes, Michelle N.; Poudrier, Johanne; Lindstedt, Ragnar; Gray, David

doi:10.1002/(sici)1521-4141(199802)28:02<548::aid-immu548>3.0.co;2-2

Cited by 71 publications

(84 citation statements)

References 49 publications

(61 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, a sIg-mediated signal transmitted following engagement of anti-IgD mAb provided additional activating signals to B cells receiving T cell help, which reduced the average division time. The possibility that this enhancement of proliferation was mediated by autocrine production of CD40L, as previously observed (38), was discounted, as the presence of an anti-CD40L mAb had no effect on proliferation induced by anti-IgD.…”

Section: Discussionmentioning

confidence: 86%

“…Recently, an alternative explanation was suggested for the effect of anti-Ig stimulation. It was proposed that murine B cells synthesize and secrete autocrine CD40L upon stimulation with anti-Ig mAbs (38). To assess whether B cell-derived CD40L was responsible for the enhancement of cell division by the 1.19 Ab, naive B cell cultures containing anti-IgD mAb with or without IL-4 were cultured for 2 days with or without a range of concentrations of the anti-CD40L hamster mAb MR1 ( Fig.…”

Section: Anti-igd Mab-mediated Enhancement Of Rcd40l-induced B Cell Dmentioning

confidence: 99%

See 1 more Smart Citation

Cross-Linking Surface Ig Delays CD40 Ligand- and IL-4-Induced B Cell Ig Class Switching and Reveals Evidence for Independent Regulation of B Cell Proliferation and Differentiation

Rush

Hasbold

Hodgkin

2002

The Journal of Immunology

View full text Add to dashboard Cite

T cells stimulate B cells to divide and differentiate by providing activating signals in the form of inducible membrane-bound molecules and secreted cytokines. Provision of these signals in vitro reproduces many of the consequences of T-B collaboration in the absence of any form of Ag stimulation. Although clearly not obligatory, Ag signals appear to play an important regulatory role in numerous aspects of the B cell response. To examine directly the effect of an Ag signal, naive B cells were stimulated in the presence of rCD40 ligand, with or without IL-4 in the presence or absence of different anti-Ig mAbs. Anti-Ig mAbs exerted variable effects on the B cell division rate, from enhancement to no effect to inhibition. In contrast, all anti-Ig mAbs tested inhibited division-linked isotype switching to IgG1 and IgE. Thus, B cell Ag receptor ligands could modify the rates of B cell expansion and class switching independently. The ability of anti-Ig reagents to modify class switching suggests the B cell Ag receptor may play an important role in the selection of Ig isotypes during T cell-dependent humoral immune responses to Ags of different physical structure.

show abstract

Section: Discussionmentioning

confidence: 86%

Section: Anti-igd Mab-mediated Enhancement Of Rcd40l-induced B Cell Dmentioning

confidence: 99%

Cross-Linking Surface Ig Delays CD40 Ligand- and IL-4-Induced B Cell Ig Class Switching and Reveals Evidence for Independent Regulation of B Cell Proliferation and Differentiation

Rush

Hasbold

Hodgkin

2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…In the mouse, hyperreactive B cells from autoimmune male BXSB mice have been shown to express CD40L (29). The induction of CD40L expression on murine B cells in vitro by anti-IgM or anti-CD38 Ab treatment has also been reported (30). Our data suggest that B cells may express functionally active CD40L, which could enhance antiviral TI responses in mice.…”

Section: Discussionmentioning

confidence: 99%

The Role of CD40-CD154 Interaction in Antiviral T Cell-Independent IgG Responses

Szomolanyi-Tsuda

Brien

Dorgan

et al. 2000

The Journal of Immunology

View full text Add to dashboard Cite

Polyomavirus (PyV) infection elicits protective T cell-independent (TI) IgG responses in T cell-deficient mice. The question addressed in this report is whether CD40 signaling plays a role in this TI antiviral IgG response. Because CD40 ligand (CD40L) can be expressed on numerous cell types in addition to activated T cells, it is possible that cells other than T cells provide CD40L to signal through CD40 on B cells and hence positively influence the antiviral TI IgG responses. In this study we show, by blocking CD40-CD40L interactions in vivo with anti-CD40L Ab treatment in TCR β×δ−/− mice and by using SCID mice reconstituted with CD40−/− B cells, that the lack of CD40 signaling in B cells results in a 50% decrease in TI IgG secreted in response to PyV. SCID mice reconstituted with CD40L−/− B cells also responded to PyV infection with diminished IgG secretion compared with that of SCID mice reconstituted with wild-type B cells. This finding suggests that B cells may provide the CD40L for CD40 signaling in the absence of T cell help during acute virus infection. Our studies demonstrate that, although about half of the TI IgG responses to PyV are independent of CD40-CD40L interactions, these interactions occur in T cell-deficient mice and enhance antiviral TI Ab responses.

show abstract

“…3) as sCD154 was previously shown to be released into the lymphocyte supernatants. 22 Supernatants from lymphocytes were shown to contain sCD154 in a variety of forms (18,33 and 66 kDa). 22 …”

Section: Scd154 Release From Renal Carcinoma Cell Linesmentioning

confidence: 99%

Expression of CD154 on renal cell carcinomas and effect on cell proliferation, motility and platelet‐activating factor synthesis

Bussolati

Russo

Deambrosis

et al. 2002

Intl Journal of Cancer

View full text Add to dashboard Cite

CD40 activation by CD154 may trigger diverse cellular responses, ranging from proliferation and differentiation to growth suppression and cell death, in normal and malignant cells. However, the pathophysiologic role of CD154 expressed by tumor cells remains unclear. We have investigated the expression of the CD40-CD154 system in 24 primary cultures derived from renal cell carcinomas, its correlation with tumor stage and its potential functional significance. We found coexpression of CD40 and CD154 in most of the renal carcinoma cell lines. CD154, but not CD40 expression, significantly correlated with tumor stage. Moreover, renal carcinoma cell lines also released the soluble form of CD154 into the supernatant. CD40 engagement by CD154 did not affect apoptosis or survival. On the contrary, CD154 stimulated cell proliferation, motility and production of PAF, a phospholipid mediator of inflammation with angiogenic properties. Key words: CD154; platelet-activating factor; renal carcinoma; CD40; angiogenesis CD154, the ligand of CD40, is a type II integral membrane protein, related to TNF and FasL. 1 Its receptor, CD40, is a 50 kDa transmembrane glycoprotein of the TNF superfamily, which is expressed in a multitude of different cell types, including B cells, monocytes, dendritic cells, endothelial cells, fibroblasts and renal epithelial cells. 2,3 CD40 was originally identified in a bladder carcinoma cell line, 4 and it is also expressed in a number of carcinomas, such as ovarian, nasopharyngeal, bladder, lung, colon and breast carcinomas, whereas normal nonproliferating tissues are CD40-negative. 5 CD40 engagement by CD154 conveys signals regulating diverse cellular responses, ranging from proliferation and differentiation to growth suppression and apoptosis. 6,7 The CD40 cytoplasmic C terminus lacks intrinsic kinase activity and adapter proteins of the TRAF family appear to mediate the activation of CD40-signaling cascades. 8 Despite the large interest, the functional role of CD40 in cancer development remains undetermined. CD40 appears to possess an opposite effect on tumor cell survival and apoptosis. CD40-mediated signaling has been reported to induce apoptosis when expressed in certain transformed cells of mesenchymal origin 9 and in carcinomas of the breast and lung. 10,11 Conversely, Jakobson et al. 12 demonstrated that CD40 stimulation inhibits Fas-mediated apoptosis in human bladder carcinoma cells and we showed a similar protective effect of CD40 in Kaposi's sarcoma cells. 13 Moreover, immunohistochemic studies revealed that detection of CD40 in primary cutaneous malignant melanoma might have negative prognostic value, suggesting its role in tumor progression. 14 CD154 is coexpressed with CD40 in melanoma cells and some carcinomas. 10,11,14 However, the pathophysiologic role of CD40 -CD154 interaction within the tumor cell remains unclear.In the present study, we investigated expression of the CD40 -CD154 system in 24 primary cultures derived from renal clear cell carcinomas, its correlation with tumor st...

show abstract

Regulation of cytoplasmic, surface and soluble forms of CD40 ligand in mouse B cells

Cited by 71 publications

References 49 publications

Cross-Linking Surface Ig Delays CD40 Ligand- and IL-4-Induced B Cell Ig Class Switching and Reveals Evidence for Independent Regulation of B Cell Proliferation and Differentiation

Cross-Linking Surface Ig Delays CD40 Ligand- and IL-4-Induced B Cell Ig Class Switching and Reveals Evidence for Independent Regulation of B Cell Proliferation and Differentiation

The Role of CD40-CD154 Interaction in Antiviral T Cell-Independent IgG Responses

Expression of CD154 on renal cell carcinomas and effect on cell proliferation, motility and platelet‐activating factor synthesis

Contact Info

Product

Resources

About