title: Adenosine production by human B cells and B cell-mediated suppression of activated T cells.
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.
authors.affiliation: University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15232, USA.
authors.forename: Zenichiro
authors.initials: Z
authors.lastname: Saze
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Schuler
authors.forename: Chang-Sook
authors.initials: CS
authors.lastname: Hong
authors.forename: Dongmei
authors.initials: D
authors.lastname: Cheng
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Jackson
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Whiteside
mesh_terms: D015720:5'-Nucleotidase / Q000235:genetics / Q000378:metabolism; D000241:Adenosine / Q000096:biosynthesis*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D001081:Apyrase / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000502:physiology*; D008213:Lymphocyte Activation / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D058851:GPI-Linked Proteins; D012333:RNA, Messenger; D018047:Receptors, Purinergic P1; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D015720:5'-Nucleotidase; C548241:NT5E protein, human; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine