Relationships between the degree of cross-linking of surface immunoglobulin and the associated inositol 1,4,5-trisphosphate and Ca2+ signals in human B cells

Abstract

Cross-linking of surface immunoglobulin (Ig) receptors on human B cells leads to the activation of a tyrosine kinase. The activated tyrosine kinase subsequently phosphorylates a number of substrates, including phospholipase C-gamma. This enzyme breaks down phosphoinositol bisphosphate to form two intracellular messengers, diacylglycerol and inositol 1,4,5-trisphosphate, leading to the activation of protein kinase C and the release of intracellular Ca2+ respectively. We have used h.p.l.c. and flow cytometry to measure accurately the inositol phosphate turnover and Ca2+ release in anti-Ig-stimulated human B cells. In particular, we have examined the effect of dose of the cross-linking antibody on the two responses. The identity of putative messenger inositol phosphates has been verified by structural analysis, and the amounts of both inositol phosphates and Ca2+ present have been quantified. In the Ramos Burkitt lymphoma, which is very sensitive to stimulus through its Ig receptors, both inositol phosphate production and Ca2+ release were found to be related to the dose of anti-Ig antibody applied. This suggests that phospholipase C-mediated signal transduction in human B cells converts the degree of cross-linking of the immunoglobulin receptor quantitatively into intracellular signals.

Transferrin Receptor Functions as a Signal‐Transduction Molecule for its Own Recycling Via Increases in the Internal Ca2 Concentration

“…The increase of [Ca"], appears to be derived from Ca" in the extracellular medium as indicated by experiments in the presence of EGTA and perhexiline. The levels of the increase we observed are moderate compared with the [Ca"], elevations described in lymphocytes using other stimuli that induce a strong stimulation of lymphocytes (McConnell et al, 1992). The [Ca"], elevation was similar to that observed with other agents, such as lowdensity lipoprotein (Schaefer et al, 1993), jacalin (Lafont et al, 1994), or, in some cells, y-interferon (Martino et al, 1994).…”

The LMP2A ITAM Is Essential for Providing B Cells with Development and Survival Signals In Vivo

“…Once activated, PLC-␥2 mediates the production of diacylglycerol and inositol trisphosphate from the PI-3K product PI(4,5)P 2 (34). Diacylglycerol is critical for activation of protein kinase C, whereas inositol trisphosphate causes a release of Ca 2ϩ from intracellular stores (56,62). Influx of Ca 2ϩ leads to activation of the calmodulin-dependent protein kinase II and the calmodulin-activated serine/theonine phosphatase calcineurin (70,77).…”

Inositol 1,3,4-Trisphosphate Acts in Vivo as a Specific Regulator of Cellular Signaling by Inositol 3,4,5,6-Tetrakisphosphate

“…D-and/or L-Ins(1,2,3,4)P 4 and Ins(1,2,3)P 3 are found in mammalian cells, the latter at concentrations of up to 10 M (15, 42, 43). These polyphosphates may be formed by dephosphorylation of InsP 6 (15,42,43). Among the inositol phosphates that we tested that contain a 2-phosphate (Table II), D/L-Ins(1,2,4)P 3 was the most potent inhibitor of the 1-kinase (IC 50 ϭ 0.7 M, Fig.…”