AUTOCRINE STIMULATION OF B-LYMPHOCYTES BY A PLATELET-ACTIVATING-FACTOR RECEPTOR AGONIST, 1-PALMITOYL-2-ACETOYL-SN-GLYCERO-3-PHOSPHOCHOLINE

Based on previous data which demonstrated the ability of platelet-acti vating factor (PAF) antagonists to inhibit constitutive immunoglobulin synthesis in B-lymphoblastoid cell lines, we determined the capacity of these cells to synthesize PAF or 1-palmitoyl-2-acetyl-sn-glycero-ph osphocholine (PAGPC), an acyl-PAF identified in various cell types. In two B-lymphoblastoid cell lines (LA350 and HSCE-), significant amount s of production of PAGPC were detected, whereas the amount of PAF was below the level of detection in our system. The biologic effects of PA GPC were examined in these cells, both of which have well-characterize d PAF receptors. PAGPC induced a concentration-dependent increase in i ntracellular Ca2+ concentrations and activation of MAP-2 kinase (as de tected by immunoblotting and measurements of kinase activity) in these cells. The kinetics and magnitude of these responses were similar to those induced by PAF, and they were inhibited by Web 2086, a PAFR anta gonist. Phosphatidylcholine, which differs from PAGPC in that it conta ins a long fatty acid residue at position 2, did not induce any of the se responses. A mutual cross-desensitization of the B lymphoblasts bet ween PAGPC and PAF was observed for Ca2+ mobilization. To induce maxim al cell stimulation, approximately 600-fold higher concentrations of P AGPC than of PAF were needed. Because the two B-lymphoblastoid cell li nes synthesized significant amounts of PAGPC, this phospholipid may pa rticipate in an autocrine stimulation pathway in B cells. Furthermore, the data indicate that PAGPC is an agonist for the PAFR in B lymphobl asts and that the ether linkage in the PAF molecule is not an absolute requirement for activity, although it increases the potency of the li gand.