B cell activation by synthetic lipopeptide analogues of bacterial lipoprotein bypassing phosphatidylinositol metabolism and proteinkinase C translocation.

Synthetic analogues of bacterial lipoprotein induce proliferation of murine small resting B lymphocytes. We investigated the role of proteinkinase C (PKC) activation in lipopeptide-induced B cell stimulation. Using a standardized extraction procedure, there was no change in membrane bound and soluble PKC activity upon stimulation with lipopeptide. However, omitting Ca2+ chelators from the standard extraction medium resulted in a decrease of membrane bound PKC activity after stimulation. Lipopeptide failed to induce phosphoinositide degradation and the generation of the two second messengers cAMP and cGMP. To test whether guanosinetriphosphate-binding proteins are involved in lipopeptide-induced signal transfer we investigated the effect of LiCl, choleratoxin and pertussistoxin on B lymphocyte proliferation. LiCl and pertussistoxin did not inhibit cell activation, whereas choleratoxin reduced the proliferation rate at concentrations higher than 0.5 micrograms/ml. Similar results were observed when LPS was used as mitogen, whereas the anti-immunoglobulin-induced B cell activation was inhibited by all three compounds. Our results show, that B cell activation by bacterial lipopeptides bypasses phosphatidylinositol metabolism and PKC translocation.