The Journal of Immunology, Vol 144, Issue 6 2351-2358, Copyright © 1990 by American Association of Immunologists

ARTICLES

Altered signal transduction secondary to surface IgM cross-linking on B- chronic lymphocytic leukemia cells. Differential activation of the phosphatidylinositol-specific phospholipase C

C Hivroz, B Geny, JC Brouet and C Grillot-Courvalin
Laboratory of Immunochemistry and Immunopathology, INSERM U. 108, Paris, France.

To further study the mechanisms by which surface Ig triggering activates the inositol phospholipid signaling pathway, we have used B cells from chronic lymphocytic leukemia patients which, as previously described, display two patterns of response upon sIg cross-linking: in one group this cross-linking induces an inositol phosphate release, an intracellular free Ca2+ concentration elevation and a subsequent cell proliferation; in a second group none of these events occur although there is an increased class II Ag expression following anti-mu stimulation as in the first group. We have been able to demonstrate that the phosphatidyl inositol specific phospholipase C (PI-PLC) can be activated in permeabilized B cells from the first group by direct stimulation, with GPT gamma S, of a guanine nucleotide binding (G) protein. In addition, since anti-mu + GTP gamma S stimulate an increased inositol phosphate production in these cells, this suggests that surface Ig cross-linking activates PI-PLC via a G protein. However, in cells from the second group no inositol phosphate is released after GTP gamma S stimulation although PI-PLC can be directly activated by high Ca2+ concentrations. This reflects in these cells, an interruption of the signaling cascade sIg/G protein/PI-PLC at the level of the G protein or at the G protein/PI-PLC coupling. In cells from both groups PMA treatment, which is known to alter phosphatidyl inositol metabolism in B cells, completely inhibits PI-PLC activation even by high Ca2+ concentrations. These studies show that the phosphatidyl inositol-dependent signaling cascade after surface Ig triggering can be altered at different levels in B cells.

This article has been cited by other articles:

				A. Rodriguez, N. Martinez, F. I. Camacho, E. Ruiz-Ballesteros, P. Algara, J.-F. Garcia, J. Menarguez, T. Alvaro, M. F. Fresno, F. Solano, et al. Variability in the Degree of Expression of Phosphorylated I{kappa}B{alpha} in Chronic Lymphocytic Leukemia Cases With Nodal Involvement Clin. Cancer Res., October 15, 2004; 10(20): 6796 - 6806. [Abstract] [Full Text] [PDF]

				S. Zupo, G. Cutrona, M. Mangiola, M. Ferrarini ;, E. Schattner, and A. Bernal Role of surface IgM and IgD on survival of the cells from B-cell chronic lymphocytic leukemia Blood, March 15, 2002; 99(6): 2277 - 2278. [Full Text] [PDF]

				A. Bernal, R. D. Pastore, Z. Asgary, S. A. Keller, E. Cesarman, H.-C. Liou, and E. J. Schattner Survival of leukemic B cells promoted by engagement of the antigen receptor Blood, November 15, 2001; 98(10): 3050 - 3057. [Abstract] [Full Text] [PDF]

				S. Sembries, H. Pahl, S. Stilgenbauer, H. Dohner, and F. Schriever Reduced Expression of Adhesion Molecules and Cell Signaling Receptors by Chronic Lymphocytic Leukemia Cells With 11q Deletion Blood, January 15, 1999; 93(2): 624 - 631. [Abstract] [Full Text] [PDF]