We have studied the expression and function of Fas antigen on murine B
lymphocytes. While Fas was present on only a few B cells in the bone
marrow, spleen, lymph node or peripheral blood, its expression could b
e strongly upregulated by stimulation with soluble CD40 ligand (CD40L)
. Treatment with anti-IgM and interleukin-4 (IL-4) alone did not induc
e significant Fas expression but enhanced CD40L-mediated up-regulation
of Fas expression. The T cell-derived signal via CD40 is therefore a
potent inducer of Fas expression by B lymphocytes. The sensitivity to
Fas-mediated apoptosis was found to depend on the duration of B cell a
ctivation. B cells activated for 1 day were resistant to Fas-mediated
cell death, whereas B cells activated for 3 days were relatively sensi
tive. Interestingly, different sensitivity to Fas-mediated death signa
l was observed in 2-day activated B cells. It was found that B cells s
timulated with CD40 L alone were more sensitive to Fas-mediated apopto
sis than were cells stimulated with CD40L plus anti-IgM or IL-4, and i
n particular, the combination of the two. The greater sensitivity exhi
bited by B cells stimulated with CD40L alone seems to be related to li
mited activation of these cells in the absence of additional stimulati
on. Co-stimulation of B cells in the presence of CD40L and anti-Fas an
tibody resulted initially in activation of B lymphocytes, as reflected
by the expression of activation markers and cell growth, but this was
followed by growth inhibition and cell death. The data demonstrate th
at the B cell response can be regulated positively and negatively by s
ignaling through CD40 and Fas antigens, respectively.