Regulation of anti-immunoglobulin-induced B lymphoma growth arrest by transforming growth factor beta 1 and dexamethasone.
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.
Gold
M R
MR
Department of Microbiology and Immunology, University of California, San Francisco 94143.
Gajewski
T F
TF
DeFranco
A L
AL
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000276:immunology; D008222:Lymphokines / Q000494:pharmacology; D016393:Lymphoma, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000276:immunology / Q000473:pathology
D000888:Antibodies, Anti-Idiotypic; D008070:Lipopolysaccharides; D008222:Lymphokines; D016212:Transforming Growth Factor beta; D003907:Dexamethasone