Modulation of anti-IgM-induced B cell apoptosis by Bcl-xL and CD40 in WEHI-231 cells. Dissociation from cell cycle arrest and dependence on the avidity of the antibody-IgM receptor interaction.

The demise of B cell progenitors expressing functional IgM receptors for self appears to be the main mechanism by which B cell tolerance is accomplished. The genetic mechanisms that regulate the death process during this critical step of B cell development are still poorly understood. We have studied the regulation of apoptosis in WEHI-231 lymphoma cells after treatment with a panel of anti-IgM mAbs as an in vitro model of clonal B cell deletion. We showed that a product of bcl-x, Bcl-xL, can inhibit anti-IgM-induced apoptosis but not cell cycle arrest in a dose-dependent manner. Bcl-xL was efficient in protecting B cells from low but not high avidity anti-IgM mAbs. In contrast to that observed with Bcl-xL, CD40 stimulation was efficient in inhibiting both cell cycle arrest and apoptosis after IgM cross-linking regardless of the binding avidity of the anti-IgM Ab. Moreover, activation through IgM receptors but not CD40 induced up-regulation followed by rapid down-modulation of Bcl-xL. Thus, the capacity of Bcl-xL to modulate anti-IgM-induced apoptosis in WEHI-231 cells is highly dependent on the avidity of the Ab-IgM receptor interaction.