By linking surface Ig to the FcR Fc gamma RII on the mouse B lymphocyt
e surface, whole anti-Ig has been shown to block cell cycle entry and
subsequent Ab production, a phenomenon called the ''Fc receptor off-si
gnal.'' IL-4 or blocking Ab to Fc gamma RII, present with whole anti-I
g, restores cell cycle progress to the levels observed with F(ab')(2)
anti-Ig. The current study demonstrates that under ''off-signal'' cond
itions with whole anti-Ig, the early entry of B cells into apoptosis w
as accelerated relative to medium alone or equimolar F(ab')(2) anti-Ig
. All reagents tested which opposed the whole-anti-Ig-induced blockade
of B cell cycle entry also protected B cells from apoptosis (IL-4, PM
A, dextran sulfate, and the monoclonal anti-Fc gamma RII 2.4G2). This
protective effect was most evident at 4 to 12 h, waning at later times
. Low dose cycloheximide partially protected B cells from whole anti-I
g-induced apoptosis, but acted as a survival factor, failing to advanc
e B cells from G(0) phase or stimulate thymidine incorporation. Additi
ve early apoptosis-associated membrane changes were transiently seen w
hen whole anti-Ig was combined with other apoptosis-accelerating agent
s (trifluoperazine, staurosporine, dexamethasone, ionomycin, high-dose
cycloheximide), but hypodiploid nuclei did not show this effect. B ce
lls from bcl-2 transgenic mice showed less apoptosis when cultured wit
h whole anti-Ig, or with any of the other agents tested. At 4 h the bc
l-2-associated reduction in hypodiploid nuclei was greater than the re
duction in membrane unpacking, but by 16 h this difference was much le
ss. These results suggest that acceleration of apoptosis contributes t
o the inhibition of proliferation induced by whole anti-Ig.