Adenosine production by human B cells and B cell–mediated suppression of activated T cells
Year: 2013
Type: article
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.
Source: Blood
Language: English
Subfield: Physiology
Domain: Life Sciences
Open Access status: green
Awards: G121953963, G1518596991, G157407396, Role of Cardiac and Renal DPP4, G233965554, G2344993196, G2450820844, G297416263, The 8-Aminopurine Hypothesis, G4136349729, The Renal 2',3'-cAMP-Adenosine Pathway, G571185835, G594213269, G6587643745, Pittsburgh Center for Kidney Research, Adenosine in Renal Sympathetic Neurotransmission, Immune Escape in Human Cancer: Mechanisms and Therapeutic Implications
OpenAlex ID: W1968862464