Biphenotypic B/macrophage cells express COX-1 and up-regulate COX-2 expression and prostaglandin E-2 production in response to proinflammatory signals

B/macrophage cells are biphenotypic leukocytes of unknown function that sim ultaneously express B lymphocyte (IgM, IgD, B220, CD5) and macrophage (phag ocytosis, F4/80, Mac-1) characteristics. B/macrophage cells can be generate d from purified mouse B lymphocytes incubated in fibroblast-conditioned med ium. A potential role for B/macrophage cells in inflammation was shown by t heir ability to express prostaglandin H synthase-1 (COX-1) and prostaglandi n H synthase-2 (COX-2) and by their production of prostaglandin (PG) E-2. C OX-1 and COX-2 mRNA expression is not observed in the precursor B lymphocyt es and is not known to be a property of B lineage cells. In contrast, COX-2 and the prostanoids PGE(2), PGF(2 alpha) and PGD(2) are highly inducible i n B/macrophage cells upon stimulation with lipopolysaccharide, CD40 ligand, or via engagement of surface IgM, supporting a role for these cells in inf lammation. PGD, and its metabolites are of interest because they activate t he nuclear receptor PPAR gamma that regulates lipid metabolism. The B/macro phage represents the first instance of a normal B-lineage cell capable of e xpressing COX-2. Importantly, B/macrophage cells were identified in vivo, p roviding 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 immuni ty.