Constitutive turnover of inositol-containing phospholipids in B220+ T cells from autoimmune-prone MRL-lpr/lpr mice.

B220+ T cells from mice that are homozygous for the lpr gene exhibit profound defects in their capacity to produce and respond to IL-2 and provide a cellular model for investigating the basic requirements for effective transmembrane signal transduction in immunologically normal T cells. A correlation between defective lectin-stimulated proliferation and deficient hydrolysis of inositol-containing phospholipids (PI) has recently been demonstrated in B220+ T cells. The finding has been postulated to explain abnormal expression of protein kinase C (PKC) activity in these cells. In a previous study, we found that the constitutive turnover of [3H]arachidonyl-PI was markedly increased in B220+ T cells from lpr-bearing MRL mice relative to that in controls. This observation suggested that an inability to metabolize PI and to generate second messengers putatively necessary for transmembrane signaling might not be responsible for aberrant PKC activity in B220+ T cells. To clarify this issue, the constitutive turnover of phosphoinositides in B220+ T cells from autoimmune-prone MRL-lpr/lpr mice was investigated. We found that in the absence of stimulation with exogenous Ag, B220+ T cells exhibited greatly increased 1) incorporation of labeled myoinositol into PI, 2) production of inositol phosphates in cells prelabeled with [3H]myoinositol, and 3) formation of diacylglycerol in [3H]arachidonic acid-labeled cells. Increased spontaneous PI turnover in B220+ cells was associated with normal phosphatidyl inositol-4,5-biphosphate-phospholipase C activity in membrane homogenates, normal levels of membrane PI, and normal resting and mitogen-stimulated levels of intracellular free-ionized Ca2+. The results suggest that an incomplete form of the PI cycle, one unassociated with PKC activation, is constitutively expressed in B220+ T cells.