Anti-immunoglobulin treatment of murine B-cell lymphomas induces active transforming growth factor β but pRB hypophosphorylation is transforming growth factor β independent

• Published in: Cell growth & differentiation Vol. 3; no. 3; pp. 175 - 181
• Main Authors: WARNER, G. L, LUDLOW, J. W, NELSON, D. A, GAUR, A, SCOTT, D. W
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.03.1992
• Subjects: Animals; Antibodies, Anti-Idiotypic; Biological and medical sciences; Cell Death - drug effects; Cell Death - physiology; Cell Division - drug effects; Hematologic and hematopoietic diseases; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, B-Cell - drug therapy; Lymphoma, B-Cell - physiopathology; Medical sciences; Mice; Phosphorylation - drug effects; Retinoblastoma Protein - metabolism; Transforming Growth Factor beta - physiology; Tumor Cells, Cultured; Animal model; Immunoglobulins; Antibody; Transforming growth factor; Rodentia; Cytokine; Malignant hemopathy; Biosynthesis; B-Lymphocyte; Lymphoma; Vertebrata; Mammalia; Mouse; Cell death; Immunotherapy
• ISSN: 1044-9523; 2377-0732

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 B-cell tolerance, we have established that these lymphomas produce active transforming growth factor beta (TGF-beta) when treated with anti-Ig and that their hierarchy of sensitivity to TGF-beta generally correlates with their growth inhibition by anti-Ig. TGF-beta, in turn, has been shown to interfere with the phosphorylation of the retinoblastoma gene product, pRB. Herein, we also demonstrate that in WEHI-231 B-lymphoma 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-beta. However, neutralizing antibodies to TGF-beta failed to prevent growth inhibition by anti-Ig in WEHI-231 and CH31. When WEHI-231 lymphoma cells were selected for growth in TGF-beta, the majority of the TGF-beta-resistant clones remained sensitive to anti-Ig-mediated growth inhibition. In these clones, the retinoblastoma gene product was found to be in the underphosphorylated form after 24-h treatment with anti-Ig, but not with TGF-beta. These data show that anti-Ig treatment of murine B-cell lymphomas stimulates the production of active TGF-beta but that a TGF-beta-independent pathway may be responsible for the pRB underphosphorylation and cell cycle blockade.