Membrane IgM cross-linking is not coupled to protein kinase C translocation in WEHI-231 B lymphoma cells
✍ Scribed by Pierre Sarthou; Nelly Henry-Toulmé; Pierre-André Cazenave
- Publisher
- John Wiley and Sons
- Year
- 1989
- Tongue
- English
- Weight
- 594 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
Membrane IgM cross-linking is not coupled to protein kinase C translocation in WEHI-231 B lymphoma cells
The early molecular events involved in the process of signal transduction via membrane immunoglobulins (mIg) include phosphatidyl inositol metabolism, intracellular Ca2+ 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, Ca2+ elevation, PKC translocation, and growth inhibition in WEHI-231 cells. Monoclonal antibodies to p and x chains of the mIgM receptor promoted a rapid increase in intracytoplasmic Ca2+ and were potent inhibitors of cell growth. Ca2+ 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 Ca2+ 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.