Regulation of bcl-xL expression and Fas susceptibility in mouse B cells by CD40 ligation, surface IgM crosslinking and IL-4.
CD40 is one of the key molecules involved in the survival, growth and differentiation of B lymphocytes. In contrast, Fas (Apo-1, CD95) mediates apoptosis of a variety of cell types, including lymphocytes. Recent studies have found that Fas expression on mouse B cells could be strongly induced by CD40 ligation, a helper T cell-derived signal. Here, evidence is provided that CD40 ligation induced two distinct signals: one leading to the upregulation of Fas and the other leading to the enhanced Fas susceptibility. B lymphoma cell lines, CH31 and WEHI279, expressed Fas on cell surfaces, but were resistant to anti-Fas antibody (Ab) induced apoptosis. Treatment with CD40 ligand (CD40L), however, greatly enhanced Fas susceptibility of these cells. Similarly, normal splenic B cells became highly susceptible to Fas-mediated apoptosis following prolonged signaling through CD40. While CD40 ligation enhanced Fas-mediated apoptosis, stimulation with anti-IgM and IL-4 partially protected CD40L-activated B cells from Fas-mediated apoptosis. It was found that bcl-xL gene expression in normal splenic B cells was induced drastically by treatment with anti-IgM and IL-4, but not CD40L. By contrast, the expression of bcl-2 or bax was not significantly affected by these treatments. Moreover, in three of the four B lymphoma cell lines tested, Fas susceptibility correlated with the status of bcl-xL expression. The data suggest that an increase in bcl-xL expression may protect B cells from Fas-mediated apoptosis.
Koizumi
T
T
Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Wang
J
J
Suzuki
Y
Y
Masuda
K
K
Watanabe
T
T
D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology*; D019254:Genes, bcl-2 / Q000276:immunology*; D007075:Immunoglobulin M / Q000378:metabolism*; D015847:Interleukin-4 / Q000494:pharmacology*; D016393:Lymphoma, B-Cell; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein; D019014:fas Receptor / Q000096:biosynthesis / Q000378:metabolism*
C494812:Bcl2l1 protein, mouse; D019013:CD40 Antigens; D007075:Immunoglobulin M; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011947:Receptors, Antigen, B-Cell; D051020:bcl-X Protein; D019014:fas Receptor; D023201:CD40 Ligand; D015847:Interleukin-4