Anti-Ig induces release of inositol 1,4,5-trisphosphate, which mediates mobilization of intracellular Ca++ stores in B lymphocytes.
Evidence from a variety of laboratories indicates that crosslinking of B cell mIg induces a rapid increase in intracellular free calcium (Ca++i). This mobilized Ca++ appears to act in concert with diacylglycerol (DAG; also released upon mIg cross-linking) to optimally activate Ca++/phospholipid-dependent protein kinase C, which plays a pivotal role in B cell activation. Here we report analysis of the source of this mobilized calcium and the mechanism responsible for its release into the cytosol. We observed the cross-linking of mIg induces the release of inositol 1,4,5-trisphosphate (InsP3), presumably as a result of action of phospholipase C on plasma membrane phosphatidylinositol 4,5-bisphosphate (PtdInsP2). The release of InsP3 and the elevation of Ca++i are coincidental, suggesting that they may be causally related. Finally, we demonstrate that submicromolar doses of InsP3 induce release of Ca++ from permeabilized cells that had preaccumulated 45Ca++ in the endoplasmic reticulum. On the basis of these findings we suggest that mIg cross-linking leads to mobilization of Ca++, in part by causing hydrolysis of PtdInsP2, yielding InsP3, which in turn causes release of calcium from the endoplasmic reticulum.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000502:physiology*; D001402:B-Lymphocytes / Q000378:metabolism*; D001826:Body Fluids / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D003432:Cross-Linking Reagents; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006868:Hydrolysis; D015544:Inositol 1,4,5-Trisphosphate; D007295:Inositol Phosphates / Q000378:metabolism* / Q000502:physiology; D007424:Intracellular Fluid / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013403:Sugar Phosphates / Q000378:metabolism*; D013997:Time Factors
D000888:Antibodies, Anti-Idiotypic; D003432:Cross-Linking Reagents; D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D013403:Sugar Phosphates; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium