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Blood. 2013 Jul 4;122(1):9-18. doi: 10.1182/blood-2013-02-482406. Epub 2013 May 15.

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

Author information

1
University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.

Abstract

Antibody-independent role of B cells in modulating T-cell responses is incompletely understood. Freshly isolated or cultured B cells isolated from the peripheral blood of 30 normal donors were evaluated for CD39 and CD73 coexpression, the ability to produce adenosine 5'-monophosphate (AMP) and adenosine (ADO) in the presence of exogenous adenosine triphosphate (ATP) as well as A₁, A2A, A2B, and A₃ adenosine receptor (ADOR) expression. Human circulating B cells coexpress ectonucleotidases CD39 and CD73, hydrolyze exogenous ATP to 5'-AMP and ADO, and express messenger RNA for A₁R, A2AR, and A₃R. 2-chloroadenosine inhibited B-cell proliferation and cytokine expression, and only A₃R selective antagonist restored B-cell functions. This suggested that B cells use the A₃R for autocrine signaling and self-regulation. Mediated effects on B-cell growth ± ADOR antagonists or agonists were tested in carboxyfluorescein diacetate succinimidyl ester assays. In cocultures, resting B cells upregulated functions of CD4⁺ and CD8⁺ T cells. However, in vitro-activated B cells downregulated CD73 expression, mainly produced 5'-AMP, and inhibited T-cell proliferation and cytokine production. These B cells acquire the ability to restrict potentially harmful effects of activated T cells. Thus, B cells emerge as a key regulatory component of T cell-B cell interactions, and their dual regulatory activity is mediated by the products of ATP hydrolysis, 5'-AMP, and ADO.

PMID:
23678003
PMCID:
PMC3701906
DOI:
10.1182/blood-2013-02-482406
[Indexed for MEDLINE]
Free PMC Article

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