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Membrane IgM cross‐linking is not coupled to protein kinase C translocation in WEHI‐231 B lymphoma cells

1989; Wiley; Volume: 19; Issue: 7 Linguagem: Inglês

10.1002/eji.1830190715

1521-4141

Pierre Sarthou, Nelly Henry‐Toulmé, Pierre‐André Cazenave,

Immune Cell Function and Interaction

Abstract The early molecular events involved in the process of signal transduction via membrane immunoglobulins (mIg) include phosphatidyl inositol metabolism, intracellular Ca 2+ mobilization, and protein kinase C (PKC) activation. Anti‐mIg antibodies exert either stimulating or inhibitory effects depending on the activation state and/or the differentiation stage of B cells. WEHI‐231 is a murine B lymphoma that becomes inactivated upon anti‐mIg treatment. This lymphoma has an immature B cell phenotype and is considered as a model for tolerance induction in B lymphocytes. In this study, we have investigated the relationship between mIg triggering, Ca 2+ elevation, PKC translocation, and growth inhibition in WEHI‐231 cells. Monoclonal antibodies to μ and χ chains of the mIgM receptor promoted a rapid increase in intracytoplasmic Ca 2+ and were potent inhibitors of cell growth. Ca 2+ elevation and PKC translocation have been previously shown to be associated in B lymphocytes. To study the subcellular distribution of PKC in WEHI‐231 cells, we used enzymatic assays and immunodetection methods. Although phorbol 12‐myristate 13‐acetate induced a rapid and almost complete redistribution of cytosolic PKC to the membrane fraction, anti‐mIg treatment failed to modify the compartmentalization of PKC. These findings extend recent observations suggesting that B cell triggering through mIg receptors may involve additional pathways independent from PKC activation. PKC activation in normal B cells is also believed to provide a regulatory signal which limits the magnitude of the early signals produced by anti‐mIg. Such a regulatory control is unlikely in WEHI‐231 cells, due to the dissociation between Ca 2+ mobilization and PKC translocation. Our findings therefore suggest that the sensitivity of immature B cells such as WEHI‐231 to the inhibitory effects of anti‐mIg antibodies may result in part from alterations of the phosphoinositide signal transduction pathway.