Differential signalling during B-cell maturation

Harnett, Margaret M.; Katz, Elad; Ford, Catriona A.

doi:10.1016/j.imlet.2004.11.002

Cited by 37 publications

(28 citation statements)

References 138 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the induction of primary necrosis of the tumor cells by PEP005 treatment (12) may be involved because primary necrosis has been shown to be immunostimulatory (48,49). PKC activation (13) may also promote dendritic cell (50) and/or B cell maturation (51). In vitro, PEP005 was able to induce release of tumoricidal reactive oxygen intermediates.…”

Section: Discussionmentioning

confidence: 99%

Neutrophils Are a Key Component of the Antitumor Efficacy of Topical Chemotherapy with Ingenol-3-Angelate

Challacombe

Suhrbier

Parsons

et al. 2006

The Journal of Immunology

154

158

View full text Add to dashboard Cite

Harnessing neutrophils for the eradication of cancer cells remains an attractive but still controversial notion. In this study, we provide evidence that neutrophils are required to prevent relapse of skin tumors following topical treatment with a new anticancer agent, ingenol-3-angelate (PEP005). Topical PEP005 treatment induces primary necrosis of tumor cells, potently activates protein kinase C, and was associated with an acute T cell-independent inflammatory response characterized by a pronounced neutrophil infiltrate. In Foxn1nu mice depleted of neutrophils and in CD18-deficient mice (in which neutrophil extravasation is severely impaired) PEP005 treatment was associated with a >70% increase in tumor relapse rates. NK cell or monocyte/macrophage deficiency had no effect on relapse rates. Both in vitro and in mice, PEP005 induced MIP-2/IL-8, TNF-α, and IL-1β, all mediators of neutrophil recruitment and activation. In vitro, PEP005 activated human endothelial cells resulting in neutrophil adhesion and also induced human neutrophils to generate tumoricidal-reactive oxygen intermediates. Treatment of tumors with PEP005 significantly elevated the level of anticancer Abs, which were able to promote neutrophil-mediated Ab-dependent cellular cytotoxicity (ADCC) in vitro. PEP005 treatment of tumors grown in SCID mice was also associated with >70% increase in tumor relapse rates. Taken together, these data suggest a central role for neutrophil-mediated ADCC in preventing relapse. PEP005-mediated cure of tumors therefore appears to involve initial chemoablation followed by a neutrophil-dependent ADCC-mediated eradication of residual disease, illustrating that neutrophils can be induced to mediate important anticancer activity with specific chemotherapeutic agents.

show abstract

Section: Discussionmentioning

confidence: 99%

Neutrophils Are a Key Component of the Antitumor Efficacy of Topical Chemotherapy with Ingenol-3-Angelate

Challacombe

Suhrbier

Parsons

et al. 2006

The Journal of Immunology

154

158

View full text Add to dashboard Cite

show abstract

“…The activation of the MAPK pathways occurs downstream of PTK activation and is a common signaling event upon TLR ligation or BCR cross-linkage (9,18). Threonine-tyrosine phosphorylation of the MAPK Erk1/2 in B cells from wild-type C57BL/6 and TLR2-deficient mice was examined.…”

Section: Porb Induces Ptk Activity and Erk1/2 Phosphorylationmentioning

confidence: 99%

“…The BCR is made up of surface Ig that is noncovalently associated with the accessory molecules Ig(␣) and Ig(␤), which are responsible for signaling. The ligation of the BCR results in tyrosine phosphorylation of Ig(␣) and Ig(␤), which go on to activate Src tyrosine kinases (18). Therefore, the blocking of PTK activity will result in the termination of the signal through the BCR's preventing proliferation.…”

Section: Vol 15 2008 Neisserial Porin-induced B-cell Signaling Evenmentioning

confidence: 99%

Role of Protein Tyrosine Kinase and Erk1/2 Activities in the Toll-Like Receptor 2-Induced Cellular Activation of Murine B Cells by Neisserial Porin

MacLeod

Bhasin

Wetzler

2008

Clin Vaccine Immunol

View full text Add to dashboard Cite

Neisserial porins are potent immune adjuvants and have been demonstrated to stimulate and induce the activation of human and murine B lymphocytes. Their immunopotentiating ability is due largely to the upregulation of the surface expression of the costimulatory ligand CD86 (B7-2) on B cells and other antigenpresenting cells. Porin-induced activation is dependent on the innate immune pattern recognition receptor Toll-like receptor 2 (TLR2). These data have led us to investigate the signal transduction events induced by PorB from Neisseria meningitidis and then, using inhibitors of these pathways, to establish the mechanism by which this bacterial major outer membrane protein induces CD86 upregulation and the proliferation of murine B cells. PorB was able to induce (i) protein tyrosine kinase (PTK) activity, (ii) the phosphorylation of Erk1 and Erk2, and (iii) IB-␣ phosphorylation, leading to NF-B nuclear translocation in B cells in a TLR2-dependent manner. PorB-induced NF-B nuclear translocation was not dependent on either PTK or Erk1/2 activities. However, B-cell proliferation and the induction of increased surface expression of CD86 by PorB were dependent on PTK activity and not Erk1/2 activation. In conclusion, PorB acts through TLR2 as a B-cell mitogen, triggering tyrosine phosphorylation of various cellular proteins that are involved in proliferation and CD86 expression, as well as the phosphorylation of Erk1/2, which is not necessary for CD86 upregulation or the proliferation of B cells.Neisserial porins are the major outer membrane proteins of the pathogenic Neisseria meningitidis, constituting approximately 60% of the outer membrane protein content (4). Neisserial outer membrane protein complexes (OMPC) act as an adjuvant in Haemophilus influenzae type b OMPC vaccines, and porins' being a significant component of the OMPC has led to their investigation as an immune adjuvant. Studies indicate that neisserial porins can induce an immune response in humans and animals in the absence of exogenous adjuvants (3,47,64,69). This adjuvanticity is demonstrated by the ability of neisserial porins to induce an immune response to poorly immunogenic substances, such as peptides (34), as well as alter the immune response to antigens like capsular polysaccharide (CPS) from a T-cell-independent response to a T-cell-dependent response (11,14,(32)(33)(34)63).The function of neisserial porins as immune adjuvants is demonstrated by the ability of porins of gram-negative bacteria to stimulate antigen-presenting cells, including B cells, and affect B-cell function (42, 54-56, 60-62, 66). Results from in vitro studies in our laboratory show that PorB from N. meningitidis can activate murine dendritic cells (DCs) and B cells by upregulating class II major histocompatibility complex (MHC) molecules and the costimulatory ligand CD86, but not CD80 (52, 66). The ability of PorB to induce DC maturation is functionally important, as further studies have demonstrated that PorB-treated DCs activate antigen-specific T cells. In addition, ...

show abstract

“…In B-cells, signaling events induced following BCR cross-link can lead to activation of several different pathways, i.e. the protein kinase C pathway, the Ca 2ϩ /calmodulin pathway, the Ras/extracellular signal-regulated kinase (ERK) pathway, and the phosphatidylinositol 3-kinase/Akt pathway (31,(33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44). Although initially described as specific cAMP-responsive factors, CREB and CREM seem to be phosphorylated by a growing number of kinases, in response to different signaling cascades (45).…”

Section: Creb Crem and Atf Transcription Factors Are Recruited To Tmentioning

confidence: 99%

Transcriptional Regulation of the Bovine Leukemia Virus Promoter by the Cyclic AMP-response Element Modulator τ Isoform

Nguyên

Walque

Veithen

et al. 2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

Bovine leukemia virus (BLV) expression is controlled at the transcriptional level through three Tax Bovine leukemia virus (BLV)7 infection is characterized by viral latency in the large majority of infected cells and by the absence of viremia. These features are thought to be due to the transcriptional repression of viral expression in vivo (1, 2). BLV transcription initiates at the unique promoter located in the 5Ј-long terminal repeat (5Ј-LTR) of the BLV genome. The 5Ј-LTR is composed of the U3, R, and U5 regions and transcription initiates at the U3-R junction. BLV exhibits two distinct functional transcriptional states as follows: a low basal level of transcription ensured by host cellular transcription factors, and a high level of transcription directed by the virus-encoded transcriptional activator Tax BLV (3,4). In the early stages of BLV transcription, before Tax BLV expression and transactivation, the basal transcriptional promoter activity is ensured by several cis-acting elements located in the 5Ј-LTR. In the U3 region are present the promoter CAAT and TATA boxes (5, 6), and three 21-bp enhancers, each containing an imperfectly conserved 8-bp cyclic AMP-responsive element (CRE), which binds at least three proteins: CRE-binding protein (CREB) and activating transcription factors 1 and 2 (ATF-1 and ATF-2) (7-10). Importantly, the 21-bp enhancers are also called Tax BLV -responsive elements (TxREs) because transactivation of the BLV LTR by Tax BLV requires these enhancers. It has been proposed that Tax BLV activation of transcription

show abstract

Differential signalling during B-cell maturation

Cited by 37 publications

References 138 publications

Neutrophils Are a Key Component of the Antitumor Efficacy of Topical Chemotherapy with Ingenol-3-Angelate

Neutrophils Are a Key Component of the Antitumor Efficacy of Topical Chemotherapy with Ingenol-3-Angelate

Role of Protein Tyrosine Kinase and Erk1/2 Activities in the Toll-Like Receptor 2-Induced Cellular Activation of Murine B Cells by Neisserial Porin

Transcriptional Regulation of the Bovine Leukemia Virus Promoter by the Cyclic AMP-response Element Modulator τ Isoform

Contact Info

Product

Resources

About