Online Purchasing Account You are logged on as Guest. LoginRegister a New AccountShopping cart (Empty)
United States 

Contribution of B cells to tumorigenesis in HIV-1-infected patients

Kaposi’s sarcoma (KS) is the most common cancer in HIV-1-infected persons. It is caused by human herpesvirus 8 (HHV-8), one of only seven human cancer viruses. KS tumor cells are primarily of endothelial cell origin. HHV-8 infection of endothelial cells is mandatory for the development of KS but it is insufficient to drive the formation of KS lesions as these cells are not fully transformed. Extensive studies suggest that this oncogenic process is linked to the latent expression of HHV-8 oncoproteins and microRNAs to promote cell proliferation and prevent apoptosis. Accumulating evidence, however, has incriminated lytic HHV-8 infection in driving HHV-8-associated cancers with persistent latent HHV-8 infection being associated with ongoing lytic virus replication. Several HHV-8 lytic proteins with homology to human proteins are thought to contribute to endothelial cell survival and proliferation by mimicking host proteins that normally regulate the cell cycle and by having immuno-modulatory effects that favor virus replication.

An unsolved enigma of KS remains in that HHV-8 latency and lytic cycle encoded factors, while unique amongst human oncogenic viruses, are insufficient to really cause cancer. An emerging hypothesis is that KS is a paracrine neoplasia in which HHV-8-infected endothelial cells depend on an abnormal excess of host cytokines and chemokines for their outgrowth. B lymphocytes are hypothesized to fundamentally contribute to this process since early studies demonstrated the presence of HHV-8-infected B cells in a large proportion of KS lesions and HHV-8 DNA in circulating B cells in patients with KS. Researchers also showed that upon pre-activation of B cells with soluble CD40L and IL-4, HHV-8 can successfully replicate in B cells in vitro.

The tumor necrosis factor (TNF) receptor family member CD40 is a critical regulator of cellular and humoral immunity. It is broadly expressed on immune cells, although predominantly on antigen-presenting cells (APCs) such as B cells and dendritic cells. One of the main functions of the CD40L/CD40 system is to provide B cells with a signal to induce proliferation, immunoglobulin class switching, antibody secretion, and rescue from apoptosis. It also has a role in the development of germinal centers and the survival of memory B cells. Although normally induced by helper T cells, CD40 signaling on B cells and other APCs can also be effectively triggered using agonistic antibodies or CD40L, thus bypassing the need for surrogates in the shape of CD4+ T helper cells. Crucially, the efficacy of CD40 signaling is dependent on the clustering of CD40 within the membrane of the targeted cells and CD40-signaling induced by soluble CD40L (sCD40L) can be potentiated up to 100-fold upon secondary crosslinking of sCD40L into higher order multimers such as Enzo’s MegaCD40L® proteins.

In a recent study conducted by Dr. Knowlton and coworkers from the University of Pittsburgh, the role of B cells on the development of Kaposi’s sarcoma (KS) was investigated. Following pre-activation of B lymphocytes with Enzo’s recombinant human soluble MegaCD40L®, they assessed HHV-8 infection and production of cytokines and chemokines. Their results showed that naive and IgM memory B cells as well as plasma cell-like populations can be infected by HHV-8 both in vitro and in the blood of subjects with KS. Importantly, virus-infected B cells are highly poly-functional, producing two to five cytokines and chemokines (i.e. IL-6, IL-8, MIP-1α, MIP-1β and TNFα) that have been postulated to enhance endothelial cell outgrowth. Altogether, these data support the hypothesis that secretion of cytokines and chemokines by HHV-8-infected B cells is central to the development of Kaposi’s and that further work is required for a complete understanding of the process and the discovery of new drugs capable of blocking this phenomenon.

Enzo Life Sciences provides immunologists and virologists with a comprehensive product portfolio to assess the immune response such as antibodies, ELISA kits and recombinant proteins; some of which are described below:

Share this TechNote

Never miss a new TechNote!

Receive our TechNotes as soon as they are published.


Follow Us!

 
comments powered by Disqus

Reference:

  1. Knowlton E. R., et al. Human herpesviruss 8 induces polyfunctional B lymphocytes that drive Kaposi's sarcoma. MBio. (2014) 5: e01277.

Related Products

IL-6 (human), ELISA kit 

ELISA, Colorimetric detection | Print as PDF
 
ADI-900-033 96 wells 461.00 USD
Do you need bulk/larger quantities?
 

IL-6 (mouse), ELISA kit 

ELISA, Colorimetric detection | Print as PDF
 
ADI-900-045 96 wells 447.00 USD
Do you need bulk/larger quantities?
 

TNF-α (mouse), ELISA kit 

ELISA, Colorimetric detection | Print as PDF
 
ADI-900-047 96 wells 467.00 USD
Do you need bulk/larger quantities?
 

TNF-α (rat), ELISA kit 

ELISA, Colorimetric detection | Print as PDF
 
ADI-900-086A 96 wells 536.00 USD
Do you need bulk/larger quantities?
 

TNF-α (human), ELISA kit 

Highly sensitive ELISA for measuring TNF-α, the primary mediator of immune regulation.
ELISA, Colorimetric detection | Print as PDF
 
ADI-900-099 96 wells 467.00 USD
Do you need bulk/larger quantities?
 

IL-8 (human), ELISA kit 

Ultrasensitive ELISA, measuring as low as 1 pg/ml of IL-8 in just 3 hours
ELISA, Colorimetric detection | Print as PDF
 
ADI-900-156 96 wells 515.00 USD
Do you need bulk/larger quantities?
 

IL-6 (human), (recombinant) 

Produced in E. coli. Non-glycosylated protein, containing 184 amino acids., ≥95% (Reducing and Non-reducing SDS-PAGE, UV spectroscopy at 280 nm) | Print as PDF
 
ALX-201-818-0020 20 µg 205.00 USD
Do you need bulk/larger quantities?
 

IL-6 (mouse), (recombinant) 

Produced in E. coli. Non-glycosylated protein, containing 187 amino acids., ≥95% (HPLC, Reducing and Non-reducing SDS-PAGE, UV spectroscopy at 280 nm) | Print as PDF
 
ALX-201-819-0010 10 µg 205.00 USD
Do you need bulk/larger quantities?
 

CD40L (soluble) (human), (recombinant) 

Increases the stimulation of B cells
Produced in E. coli. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to a linker peptide (6 aa) and a FLAG®-tag., ≥95% (SDS-PAGE), ELISA | Print as PDF
 
ALX-522-015-C010 10 µg 163.00 USD
 
ALX-522-015-2010 2x10 µg 222.00 USD
 
ALX-522-015-6010 6x10 µg SuperPack 543.00 USD
Do you need bulk/larger quantities?
 

CD40 (human):Fc (human), (recombinant) 

Produced in HEK 293 cells. The cysteine-rich region (aa 21-193) of human CD40 is fused to the Fc portion of human IgG1., ≥95% (SDS-PAGE), ELISA | Print as PDF
 
ALX-522-016-C050 50 µg 370.00 USD
Do you need bulk/larger quantities?
 

CD40 (human):COMP (human), (recombinant) 

First non-antibody blocker of CD40L signalling
Produced in HEK 293 cells. The extracellular domain of human CD40 (aa 1-193) is fused to a FLAG®-tag at the N-terminus and to human cartilage oligomeric matrix protein (COMP, aa 32-80) at the C-terminus., ≥90% (SDS-PAGE) | Print as PDF
 
ALX-522-064-C010 10 µg 425.00 USD
Do you need bulk/larger quantities?
 

CD40L (soluble) (mouse), (recombinant) 

Produced in HEK 293 cells. The extracellular domain of mouse CD40L (CD154) (aa 115-260) is fused at the N-terminus to a linker peptide (8 aa) and a FLAG®-tag., ≥90% (SDS-PAGE), ELISA | Print as PDF
 
ALX-522-070-C010 10 µg 240.00 USD
 
ALX-522-070-2010 2x10 µg 431.00 USD
Do you need bulk/larger quantities?
 

Fc (human):CD40L (soluble) (mouse), (recombinant) 

Produced in HEK 293 cells. The extracellular domain of mouse CD40L (CD154) (aa 115-260) is fused at the N-terminus to the Fc portion of human IgG1 and a linker peptide (20 aa)., ≥90% (SDS-PAGE), ELISA | Print as PDF
 
ALX-522-072-C010 10 µg 414.00 USD
Do you need bulk/larger quantities?
 

Fc (human):CD40L (soluble) (human), (recombinant) 

Produced in HEK 293 cells. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to the Fc portion of human IgG1 and a linker peptide (20 aa)., ≥90% (SDS-PAGE), ELISA, FUNC | Print as PDF
 
ALX-522-076-C010 10 µg 425.00 USD
Do you need bulk/larger quantities?
 

MEGACD40L® (soluble) (human), (recombinant) 

High activity, high purity CD40L protein for co-stimulatory activation of an immune response
Produced in CHO cells. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to mouse ACRP30headless (aa 18-111) and a FLAG®-tag., ≥90% (SDS-PAGE) | Print as PDF
 
ALX-522-110-C010 10 µg 499.00 USD
Do you need bulk/larger quantities?
 

MEGACD40L® (soluble) (mouse), (recombinant) 

Highly active
Produced in CHO cells. The extracellular domain of mouse CD40L (CD154) (aa 115-260) is fused at the N-terminus to mouse ACRP30headless (aa 18-111) and a FLAG®-tag., ≥95% (SDS-PAGE) | Print as PDF
 
ALX-522-120-C010 10 µg 525.00 USD
Do you need bulk/larger quantities?
 

CD40L (mouse) monoclonal antibody (MR1) 

FUNC | Print as PDF
 
ALX-804-331-C100 100 µg 273.00 USD
 
ALX-804-331-C500 500 µg 539.00 USD
Do you need bulk/larger quantities?
 

CD40L (human) monoclonal antibody (blocking) (MK13A4) 

Flow Cytometry, FUNC | Print as PDF
 
ALX-805-037-C100 100 µg Purified 291.00 USD
Do you need bulk/larger quantities?
 

CD40 (mouse) monoclonal antibody (FGK45) 

Flow Cytometry, FUNC | Print as PDF
 
ALX-805-046-C100 100 µg 184.00 USD
 
ALX-805-046-C500 500 µg 539.00 USD
Do you need bulk/larger quantities?
 

CD40L, soluble (human) (recombinant) set 

Ligand plus enhancer for improved stability and enhanced immune activation.
Produced in E. coli. The extracellular domain of human CD40L (CD154) (aa 116-261) is fused at the N-terminus to a linker peptide (6 aa) and a FLAG®-tag., ≥95% (SDS-PAGE)., FUNC | Print as PDF
 
ALX-850-064-KI01 1 Set 505.00 USD
Do you need bulk/larger quantities?
 

CD40L, soluble (mouse) (recombinant) set 

Produced in HEK 293 cells. The extracellular domain of mouse CD40L (CD154) (aa 115-260) is fused at the N-terminus to a linker peptide (8 aa) and a FLAG®-tag., ≥90% (SDS-PAGE)., ELISA, FUNC | Print as PDF
 
ALX-850-075-KI01 1 Set 614.00 USD
Do you need bulk/larger quantities?
 

CD40, soluble (human) ELISA kit 

ELISA | Print as PDF
 
ALX-850-262-KI01 96 wells 689.00 USD
Do you need bulk/larger quantities?
 

CD40L, soluble (human) ELISA kit (high sensitivity) 

ELISA | Print as PDF
 
ALX-850-311-KI01 96 wells 689.00 USD
Do you need bulk/larger quantities?
 

CD40 (human) monoclonal antibody (G28-5) 

Flow Cytometry, IHC (PS), FUNC | Print as PDF
 
ENZ-ABS130-0100 100 µg 423.00 USD
Do you need bulk/larger quantities?
 

CD40 (human) monoclonal antibody (mAb 89) 

Flow Cytometry, IHC (PS), FUNC | Print as PDF
 
ENZ-ABS148-0100 100 µg 353.00 USD
Do you need bulk/larger quantities?
 

IL-8 (human), (recombinant) 

Produced in E. coli., ≥98% (SDS & HPLC) | Print as PDF
 
ENZ-PRT185-0025 25 µg 202.00 USD
Do you need bulk/larger quantities?
 

Recommend this page

 
For Research Use Only. Not for use in diagnostic procedures.
Keep in touch

©2017 Enzo Life Sciences, Inc.,