MODULATION OF ANTI-IGM-INDUCED B-CELL APOPTOSIS BY BCL-X(L) AND CD40 IN WEHI-231 CELLS - DISSOCIATION FROM CELL-CYCLE ARREST AND DEPENDENCEON THE AVIDITY OF THE ANTIBODY-IGM RECEPTOR INTERACTION

The demise of B cell progenitors expressing functional IgM receptors f or self appears to be the main mechanism by which B cell tolerance is accomplished. The genetic mechanisms that regulate the death process d uring this critical step of B cell development are still poorly unders tood. 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 mo del of clonal B cell deletion. We showed that a product of bcl-x, Bcl- x(L), can inhibit anti-IgM-induced apoptosis but not cell cycle arrest in a dose-dependent manner, Bcl-x, was efficient in protecting B cell s from low but not high avidity anti-IgM mAbs, In contrast to that obs erved with Bcl-x(L), 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 dow n-modulation of Bcl-x(L). Thus, the capacity of Bcl-x(L) to modulate a nti-IgM-induced apoptosis in WEHI-231 cells is highly dependent on the avidity of the Ab-IgM receptor interaction.