Adenosine production by human B cells and B cell–mediated suppression of activated T cells

Saze, Zenichiro; Schuler, Patrick J.; Hong, Chang‐Sook; Cheng, Dongmei; Jackson, Edwin K.; Whiteside, Theresa L.

doi:10.1182/blood-2013-02-482406

Cited by 213 publications

(234 citation statements)

References 32 publications

Supporting

Mentioning

221

Contrasting

Unclassified

Order By: Relevance

“…There remained a possibility that 5 0 -AMP produced in excess by CD39 high B cells and reported to be able to signal via the A 1 R 10 had stimulatory autocrine effects on proliferation of these cells. In a series of experiments with pharmacologic agonists and antagonists of A 1 R, A 2A R and A 3 R (but not of A 2B R which is not expressed in B cells 14 ) we showed that only A 2A R antagonist, ZM241385, significantly (p < 0.001) decreased both proliferation and CD39 expression in CD39 high B cells (Fig. 4E, F).…”

Section: Proliferation Of Cd39 High B Cellsmentioning

confidence: 91%

“…Coexpression of active ectonucleotidases, CD39 and CD73, in resting circulating B cells suggests they can hydrolyze eATP, yielding 5 0 -AMP and ADO. 14 We have recently reported that in vitro activation of human B cells with CD40L and IL-4 leads to significant upregulation of surface CD39 expression levels and of its enzymatic activity. 14 While CD73 surface expression was not measurably increased, ADO production by these activated B cells also increased and translated into upregulated immunosuppression of Teff functions.…”

Section: Discussionmentioning

confidence: 99%

“…13 Our recent study shows that upon in vitro activation, human CD19 C B cells inhibit Teff proliferation; in contrast, resting B cells promote Teff proliferation. 14 T-cell suppression by activated B cells is associated with upregulation of CD39 on the B-cell surface. 14 Activated B cells in the presence of eATP upregulate CD39 but downregulate CD73 expression and mainly produce 5 0 -AMP but little ADO.…”

Section: Introductionmentioning

confidence: 99%

“…14 T-cell suppression by activated B cells is associated with upregulation of CD39 on the B-cell surface. 14 Activated B cells in the presence of eATP upregulate CD39 but downregulate CD73 expression and mainly produce 5 0 -AMP but little ADO. 14 Nevertheless, these B cells inhibit T-cell proliferation and cytokine production by a mechanism presumably driven by 5 0 -AMP signaling.…”

Section: Introductionmentioning

confidence: 99%

“…14 Activated B cells in the presence of eATP upregulate CD39 but downregulate CD73 expression and mainly produce 5 0 -AMP but little ADO. 14 Nevertheless, these B cells inhibit T-cell proliferation and cytokine production by a mechanism presumably driven by 5 0 -AMP signaling. 14 As 5 0 -AMP was reported to be an A 1 R agonist, 10 we surmise that functions of A 1 R C T cells are inhibited not only by ADO via A 2A R but also by B cell-derived 5 0 -AMP signaling via the A 1 R. The molecular mechanisms involved in the ATP-driven suppression of T-cell functions by B cells remain poorly understood, and the identity of Breg responsible for this effect and their characteristics remain unclear.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Phenotypic and functional characteristics of CD39^highhuman regulatory B cells (Breg)

et al. 2016

View full text Add to dashboard Cite

CD39 and CD73 are key enzymes in the adenosine (ADO) pathway. ADO modulates pathophysiological responses of immune cells, including B cells. It has recently emerged that a subpopulation of ADOproducing CD39 C CD73 C B cells has regulatory properties. Here, we define the CD39 high subset of these cells as the major contributor to the regulatory network operated by human B lymphocytes. Peripheral blood B cells were sorted into CD39 neg , CD39 inter and CD39 high subsets. The phenotype, proliferation and IL-10 secretion by these B cells were studied by flow cytometry. 5 0 -AMP and ADO levels were measured by mass spectrometry. Agonists or antagonists of A 1 R, A 2A R and A 3 R were used to study ADO-

show abstract

Section: Proliferation Of Cd39 High B Cellsmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Phenotypic and functional characteristics of CD39^highhuman regulatory B cells (Breg)

et al. 2016

View full text Add to dashboard Cite

show abstract

Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients

Ibrahim

Aly

Morath

et al. 2021

Immunity Inflam & Disease

View full text Add to dashboard Cite

Objectives Regulatory B cells (Bregs) and T cells (Tregs) are thought to be involved in the regulation of graft acceptance in renal transplant recipients. However, mechanisms that affect Breg differentiation and interaction with Tregs are rather unclear. Methods Using eight‐color‐fluorescence flow cytometry, Tregs and CD19+ CD24hiCD38hi Bregs were analyzed in whole blood samples of 80 stable kidney transplant recipients, 20 end‐stage renal disease (ESRD) patients and 32 healthy controls (HC). In addition, differentiation of Bregs and Tregs was studied in different micromilieus using cocultures with strongly enriched B‐lymphocytes and autologous peripheral blood mononuclear cells stimulated with CpG and phytohemagglutinin. Results Bregs were higher in HC than in ESRD patients and lowest in transplant recipients. Bregs were higher early as compared to late posttransplant. Posttransplant, high Bregs were associated with higher glomerular filtration rate (GFR) and lower C‐reactive protein (CRP). Higher doses and blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil as well as higher doses of steroids were not associated with low Bregs. In contrast, most Treg subsets were lower when blood levels of ciclosporine, tacrolimus, and mycophenolate mofetil were higher. Tregs were not associated with Bregs, GFR, CRP plasma levels, and occurrence of rejection or infection. In vitro, differentiation of Bregs was strongly dependent on T cell support and was blocked by excessive or lacking T‐cell help. Tregs were not associated with Breg numbers in vitro. Conclusion Bregs appear to be insensitive to high doses of posttransplant immunosuppressive drugs. The protracted Breg decrease posttransplant might be caused by impaired T cell support attributable to immunosuppressive drugs.

show abstract

B cells promote tumor progression in a mouse model of HPV‐mediated cervical cancer

Tang

Dadaglio

Oberkampf

et al. 2016

Intl Journal of Cancer

View full text Add to dashboard Cite

Enhancing anti-tumor immunity and preventing tumor escape are efficient strategies to increase the efficacy of therapeutic cancer vaccines. However, the treatment of advanced tumors remains difficult, mainly due to the immunosuppressive tumor microenvironment. Regulatory T cells and myeloid-derived suppressor cells have been extensively studied, and their role in suppressing tumor immunity is now well established. In contrast, the role of B lymphocytes in tumor immunity remains unclear because B cells can promote tumor immunity or display regulatory functions to control excessive inflammation, mainly through IL-10 secretion. Here, in a mouse model of HPV-related cancer, we demonstrate that B cells accumulated in the draining lymph node of tumor-bearing mice, due to a prolonged survival, and showed a decreased expression of MHC class II and CD86 molecules and an increased expression of Ly6A/E, PD-L1 and CD39, suggesting potential immunoregulatory properties. However, B cells from tumor-bearing mice did not show an increased ability to secrete IL-10 and a deficiency in IL-10 production did not impair tumor growth. In contrast, in B cell-deficient μMT mice, tumor rejection occurred due to a strong T cell-dependent anti-tumor response. Genetic analysis based on single nucleotide polymorphisms identified genetic variants associated with tumor rejection in μMT mice, which could potentially affect reactive oxygen species production and NK cell activity. Our results demonstrate that B cells play a detrimental role in anti-tumor immunity and suggest that targeting B cells could enhance the anti-tumor response and improve the efficacy of therapeutic cancer vaccines.

show abstract

Adenosine production by human B cells and B cell–mediated suppression of activated T cells

Cited by 213 publications

References 32 publications

Phenotypic and functional characteristics of CD39^highhuman regulatory B cells (Breg)

Phenotypic and functional characteristics of CD39^highhuman regulatory B cells (Breg)

Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients

B cells promote tumor progression in a mouse model of HPV‐mediated cervical cancer

Contact Info

Product

Resources

About

Adenosine production by human B cells and B cell–mediated suppression of activated T cells

Cited by 213 publications

References 32 publications

Phenotypic and functional characteristics of CD39highhuman regulatory B cells (Breg)

Phenotypic and functional characteristics of CD39highhuman regulatory B cells (Breg)

Relationship of transitional regulatory B and regulatory T cells and immunosuppressive drug doses in stable renal transplant recipients

B cells promote tumor progression in a mouse model of HPV‐mediated cervical cancer

Contact Info

Product

Resources

About

Phenotypic and functional characteristics of CD39^highhuman regulatory B cells (Breg)

Phenotypic and functional characteristics of CD39^highhuman regulatory B cells (Breg)