Regulation of bcl-x(L) expression and Fas susceptibility in mouse B cells by CD40 ligation, surface IgM crosslinking and IL-4

Toshiki Koizumi, Jiyang Wang, Yasuhiro Suzuki, Keiji Masuda, Takeshi Watanabe

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Abstract

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 WEH1279, 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-x(L) 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-x(L) expression. The data suggest that an increase in bcl-x(L) expression may protect B cells from Fas-mediated apoptosis.

Original languageEnglish
Pages (from-to)1247-1253
Number of pages7
JournalMolecular Immunology
Volume33
Issue number16
DOIs
Publication statusPublished - Nov 1 1996

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All Science Journal Classification (ASJC) codes

  • Immunology
  • Molecular Biology

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