SIGNALING PROPERTIES OF ANTIIMMUNOGLOBULIN - RESISTANT VARIANTS OF WEHI-231 B-LYMPHOMA-CELLS

Stimulation of the B cell antigen receptor (BCR) of the murine immatur e WEHI-231 B lymphoma with anti-immunoglobulin antibodies leads to irr eversible growth arrest and apoptosis. As in normal B cells, membrane immunoglobulin (mIg) ligation in WEHI-231 cells triggers a series of s ignaling cascades from the BCR to intracellular compartments. In order to address the role of early signals in mediating the growth arrest o f WEHI-231 cells, we have generated two variants resistant to the anti -Ig-mediated inhibitory effect. Some of the properties of these varian ts have been recently described in terms of bcl-2 and c-myc gene regul ation. We report here that these variants can be further distinguished from the wild type on the basis of significant alterations in the ear ly biochemical events which follow mIg ligation. Both Ca2+ signals and patterns of protein tyrosine phosphorylation were affected in these v ariants, suggesting that alterations in the early signal transduction machinery may have profound effects on the fate of B cells. In additio n, we found that expression of the p75(HS1) substrate of p53/56(lyn) w as strikingly reduced in both variants as compared to the wild type. T hese findings support the view that p75(HS1) may play a critical role in BCR-dependent signaling cascades.