Regulation of B-cell development by COX-1. IL-7 receptor engagement on pro-B cells triggers JAK/STAT5 signaling, resulting in translocation of STAT5 to the nucleus and transcription of target genes. These include the master transcription factor Pax5, which drives the pro-B to pre-B cell transition. COX-1 is expressed at high levels in pro-B cells, where it catalyzes the production of TxA₂. Released TxA₂ triggers its receptor TP in a cell autonomous manner, promoting the accumulation of cAMP and activation of PKA, which enhances JAK3/STAT5 signaling and Pax5 expression, thereby cooperating with the IL-7 receptor in driving the pro-B to pre-B maturation step. COX-1 inhibition by aspirin (ASA) in healthy volunteers results in a reduction in TxA₂ production, which correlates with impaired JAK3/STAT5 signaling and Pax5 expression. Professional illustration by Laura Patrussi.