Anti - Immunoglobulin Treatment of Murine B - Cell Lymphomas Induces Active Transforming Growth Factor 9 but pRB Hypophosphorylation Is Trans - forming Growth

Abstrad Cross-linking of B-cell membrane immunoglobulin (Ig) receptors induces growth arrest at G1-S, leading to apoptosis and cell death in the immature lymphomas WEHI-231 and CH31, but not in the CH12 B-cell line. In this system, which has been used as a model for Bcell tolerance, we have established that these lymphomas produce adive transforming growth fador (TGF8) when treated with anti-Ig and that their hierarchy of sensitivity to TGF-fi generally correlates with their growth inhibition by anti-Ig. TGF-$, in turn, has been shown to interfere with the phosphorylation of the retinoblastoma gene produd, pRB. Herein, we also demonstrate that in WEHI-231 B-Iymphoma cells treated with anti-Ig for 24 h, the pRB protein is found to be predominantly in the underphosphorylated form, as previously reported for cells arrested by the exogenous addition of TGF-fl. However, neutralizing antibodies to TGFfailed to prevent growth inhibition by anti-Ig in WEHI-231 and CH31. When WEHI-231 lymphoma cells were selected for growth in TGF-fl, the majority of the TGF-ft-resistant clones remained sensitive to anti-Ig-mediated growth inhibition. In these clones, the retinoblastoma gene produd was found to be in the underphosphorylated form after 24-h treatment with anti-Ig, but not with TGF-$. These data show that anti-Ig treatment of murine B-cell lymphomas stimulates the produdion of active TGF-$ but that a TGF-fl-independent pathway may be responsible for the pRB underphosphorylation and cell cycle blockade.