Signaling properties of anti-immunoglobulin--resistant variants of WEHI-231 B lymphoma cells.
Stimulation of the B cell antigen receptor (BCR) of the murine immature WEHI-231 B lymphoma with anti-immunoglobulin antibodies leads to irreversible growth arrest and apoptosis. As in normal B cells, membrane immunoglobulin (mIg) ligation in WEHI-231 cells triggers a series of signaling cascades from the BCR to intracellular compartments. In order to address the role of early signals in mediating the growth arrest of WEHI-231 cells, we have generated two variants resistant to the anti-Ig-mediated inhibitory effect. Some of the properties of these variants have been recently described in terms of bcl-2 and c-myc gene regulation. We report here that these variants can be further distinguished from the wild type on the basis of significant alterations in the early biochemical events which follow mIg ligation. Both Ca2+ signals and patterns of protein tyrosine phosphorylation were affected in these variants, suggesting that alterations in the early signal transduction machinery may have profound effects on the fate of B cells. In addition, we found that expression of the p75HS1 substrate of p53/56lyn was strikingly reduced in both variants as compared to the wild type. These findings support the view that p75HS1 may play a critical role in BCR-dependent signaling cascades.
Benhamou
L E
LE
Unité d'Immunochimie Analytique, CNRS URA 359, Institut Pasteur, Paris, France.
Watanabe
T
T
Kitamura
D
D
Cazenave
P A
PA
Sarthou
P
P
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000276:immunology; D005434:Flow Cytometry; D007136:Immunoglobulins / Q000276:immunology*; D008213:Lymphocyte Activation; D016393:Lymphoma, B-Cell / Q000276:immunology; D051379:Mice; D011233:Precipitin Tests; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000888:Antibodies, Anti-Idiotypic; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; D002118:Calcium