Activation signals generated through surface Ig (slg)1 on B lymphocytes are transduced across the plasma membrane partially or entirely through G protein-linked phospholipase C catalyzed hydrolysis of inositol phospholipids (PI) (1-5). Metabolites ofthis process act as intracellular "second messengers" to initiate signaling pathways which then synergize to eventually result in transition from the resting state (Go) into cell cycle (Go-to-Gi transition) (6) .The linkage of downstream activation events to PI hydrolysis has been inferred from studies using pharmacologic agents that either mimic or inhibit PI hydrolysis. For example, activation of protein kinase C by phorbol diesters upregulates class II antigen expression, induces cfos gene expression (7,8) and synergizes with Cat+ ionophores to drive B lymphocytes into cell cycle (6). Conversely, neomycin inhibition of PI hydrolysis blocks anti-Ig stimulated release of sequestered Cat+, as well as Cat + influx (9). Through such studies, signaling pathways have been constructed that link sIg-generated signals to short-term physiologic changes, changes in gene expression, and long-term adaptive responses (10, 11).Transformed B cell lines representative of specific maturation stages have proven useful for studies ofreceptor Ig signal transduction . For example, the murine B lymphoma WEHI-231 displays signal transduction events similar to normal B lymphocytes with respect to G protein-linked PI hydrolysis (2, 12), Cat+ mobilization (13-15), protein phosphorylation (16), and induction of cfos (8) and c-myc (17, 18) expression. The coupling oflater events in WEHI-231 appears different from normal mature B lymphocytes, since sIg-generated signals are translated by WEHI-231 to cause decreased proliferation and eventually cell death (19,20).We describe here a system for further exploring sIg signaling and verifying proposed linkages between activation events and downstream processes. We have generated a sIgM signaling variant ofWEHI-231 that continues to express high levels of sIgM but is refractory to sIgM-generated downregulatory signals.