Activation of the phosphatidylinositol metabolic pathway by low molecular weight B cell growth factor.
The possible role of phosphatidylinositol breakdown in the induction of proliferation of human activated B cells by low molecular weight B cell growth factor (LMW-BCGF) was examined. LMW-BCGF was found to induce a rapid rise in the concentration of inositol trisphosphate (InsP3) in [3H]inositol-loaded B cell blasts, obtained by prior anti-mu antibody activation. A concomitant decrease in the concentration of phosphatidylinositol 4,5-bisphosphate could be detected at the same time. Maximum generation of InsP3 occurred within 15-30 s after the addition of the LMW-BCGF ligand to the activated B cells, then was followed by a slow decrease and return to control values. The amount of InsP3 generated by phosphatidylinositol hydrolysis was dependent on the concentration of LMW-BCGF. This effect was only detected in B cells already preactivated by a first signal such as anti-mu antibody and not in resting unstimulated B cells. In contrast, under similar conditions, interleukin 2, another B cell growth-promoting lymphokine, did not alter the rate of formation of the various phosphatidylinositol breakdown products. An augmentation of the [Ca2+]i concentration was also detected in activated B cells upon addition of LMW-BCGF and this increase could be blocked by TMB-8, a specific inhibitor of endoplasmic reticulum calcium release. Hydrolysis of phosphoinositides thus represents an essential component in the mechanism of transduction of the signal provided by LMW-BCGF.
Renard
D
D
U 274 INSERM Physiologie et Pharmacologie Cellulaire, Orsay, France.
Petit-Koskas
E
E
Génot
E
E
Dugas
B
B
Poggioli
J
J
Kolb
J P
JP
D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000378:metabolism / Q000502:physiology*
D007295:Inositol Phosphates; D007378:Interleukins; D008222:Lymphokines; D010716:Phosphatidylinositols; C058162:low molecular weight-B cell growth factor; D015847:Interleukin-4; D004247:DNA; D002118:Calcium