Cross-linking membrane IgM induces production of inositol trisphosphate and inositol tetrakisphosphate in WEHI-231 B lymphoma cells.
The addition of anti-IgM to the immature B lymphoma cell line WEHI-231 resulted in breakdown of phosphatidylinositol 4,5-bisphosphate, generating diacylglycerol and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3). These reactions have recently been demonstrated in mature resting B cells stimulated with anti-IgM, as well. In addition to Ins(1,4,5)P3, inositol tetrakisphosphate (InsP4) and inositol 1,3,4-trisphosphate (Ins(1,3,4)P3) were rapidly generated in WEHI-231 cells upon stimulation of the antigen receptor with anti-IgM. These two inositol polyphosphates are probably generated from Ins(1,4,5)P3 by phosphorylation to yield InsP4 and removal of the 5-phosphate from InsP4 to yield Ins(1,3,4)P3. It is possible that these inositol polyphosphates play a second messenger role in mediating the biologic effects of antigen-receptor signaling. It had previously been shown that anti-IgM also causes an increase in cytoplasmic free calcium. Therefore, the relationship between Ca2+ elevation and phosphoinositide breakdown was investigated. Although elevation of cytoplasmic Ca2+ with ionophores can trigger phosphoinositide breakdown, this required levels of Ca2+ well beyond those normally seen in response to anti-IgM. Thus, the Ca2+ elevation seen in response to anti-IgM cannot be the event controlling phosphoinositide breakdown. WEHI-231 cells have been shown to have a calcium storage compartment that releases Ca2+ in the presence of Ins(1,4,5)P3; therefore, it is likely that anti-IgM stimulates phosphoinositide breakdown as a primary event and this leads to the elevation of cytoplasmic Ca2+.
D000818:Animals; D000888:Antibodies, Anti-Idiotypic; D001402:B-Lymphocytes / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D007075:Immunoglobulin M / Q000502:physiology*; D007295:Inositol Phosphates / Q000378:metabolism*; D007536:Isomerism; D008223:Lymphoma; D051379:Mice; D010716:Phosphatidylinositols / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology*; D013403:Sugar Phosphates / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D007075:Immunoglobulin M; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011947:Receptors, Antigen, B-Cell; D013403:Sugar Phosphates; D002118:Calcium