B/macrophage cells are biphenotypic leukocytes of unknown function that simultaneously express B lymphocyte (IgM, IgD, B220, CD5) and macrophage (phagocytosis, F4/80, Mac-1) characteristics. B/macrophage cells can be generated from purified mouse B lymphocytes incubated in fibroblast-conditioned medium. A potential role for B/macrophage cells in inflammation was shown by their ability to express prostaglandin H synthase-1 (COX-1) and prostaglandin H synthase-2 (COX-2) and by their production of prostaglandin (PG) E 2 . COX-1 and COX-2 mRNA expression is not observed in the precursor B lymphocytes and is not known to be a property of B lineage cells. In contrast, COX-2 and the prostanoids PGE 2 , PGF 2 Β§ and PGD 2 are highly inducible in B/macrophage cells upon stimulation with lipopolysaccharide, CD40 ligand, or via engagement of surface IgM, supporting a role for these cells in inflammation. PGD 2 and its metabolites are of interest because they activate the nuclear receptor PPAR + that regulates lipid metabolism. The B/macrophage represents the first instance of a normal B-lineage cell capable of expressing COX-2. Importantly, B/macrophage cells were identified in vivo, providing evidence that they may play a significant role in immune responses. Since PGE 2 blunts IL-12 production, its synthesis by B/macrophage cells may shift the balance of an immune response towards Th2 and humoral immunity.