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Regulation of anti-immunoglobulin-induced B lymphoma growth arrest by transforming growth factor beta 1 and
M R Gold1, T F Gajewski, A L DeFranco
1Department of Microbiology and Immunology, University of California, San Francisco 94143.
Exposure of the murine B lymphoma cell line WEHI-231 to anti-immunoglobulin M (anti-IgM) antibodies results in growth arrest in the G1 phase of the cell cycle followed by programmed cell death. This response may be analogous to the clonal deletion of immature B cells that occurs when the membrane IgM on these cells is engaged by self-antigens or by anti-IgM antibodies. Thus the WEHI-231 cell line has been a useful in vitro system for identifying factors that modulate anti-Ig-induced growth inhibition and/or clonal deletion. For example, both antigen-induced tolerance induction in immature B cells and anti-Ig-induced growth arrest of WEHI-231 cells are prevented by bacterial lipopolysaccharide or by the products of activated T helper cells. Since negative signaling by membrane Ig may also be regulated by additional factors, we asked whether other cytokines or hormones would regulate the growth of WEHI-231 cells or its response to anti-IgM antibodies. We show here that two compounds that are generally immunosuppressive, transforming growth factor beta 1 (TGF-beta 1) and the synthetic corticosteroid, dexamethasone, blocked the ability of lipopolysaccharide and T cell-derived lymphokines to protect WEHI-231 cells from anti-IgM-induced growth arrest. In addition, TGF-beta 1 and dexamethasone slightly inhibited the growth of WEHI-231 cells by themselves and also potentiated the growth inhibitory effects of anti-IgM antibodies. Thus for WEHI-231 cells, TGF-beta 1 and dexamethasone are inhibitory factors which favor growth arrest.
Exposure of the murine B lymphoma cell line WEHI-231 to anti-immunoglobulin M (anti-IgM) antibodies results in growth arrest in the G1 phase of the cell cycle followed by programmed cell death. This response may be analogous to the clonal deletion of immature B cells that occurs when the membrane IgM on these cells is engaged by self-antigens or by anti-IgM antibodies. Thus the WEHI-231 cell line has been a useful in vitro system for identifying factors that modulate anti-Ig-induced growth inhibition and/or clonal deletion. For example, both antigen-induced tolerance induction in immature B cells and anti-Ig-induced growth arrest of WEHI-231 cells are prevented by bacterial lipopolysaccharide or by the products of activated T helper cells. Since negative signaling by membrane Ig may also be regulated by additional factors, we asked whether other cytokines or hormones would regulate the growth of WEHI-231 cells or its response to anti-IgM antibodies. We show here that two compounds that are generally immunosuppressive, transforming growth factor beta 1 (TGF-beta 1) and the synthetic corticosteroid, dexamethasone, blocked the ability of lipopolysaccharide and T cell-derived lymphokines to protect WEHI-231 cells from anti-IgM-induced growth arrest. In addition, TGF-beta 1 and dexamethasone slightly inhibited the growth of WEHI-231 cells by themselves and also potentiated the growth inhibitory effects of anti-IgM antibodies. Thus for WEHI-231 cells, TGF-beta 1 and dexamethasone are inhibitory factors which favor growth arrest.