A schematic of signaling between a resting (freshly harvested) B cell or an activated (precultured with IL-4 and CD-40L) B cell and a T cell stimulated with anti-CD3/anti-CD28 Abs via the TCR. Note that ADO produced by resting B cells primarily exerts autocrine regulation, downmodulating B-cell functions via the A3R. Activated Teff cells rich in ADO deaminase hydrolyze ADO to inosine (INO) and thus avoid inhibition. In contrast, activated B cells enriched in ADO deaminase hydrolyze ADO to inosine and largely produce 5′-AMP, which binds to A1R on activated Teff and inhibits their functions.