TOLERANT B-LYMPHOCYTES ACQUIRE RESISTANCE TO FAS-MEDIATED APOPTOSIS AFTER TREATMENT WITH INTERLEUKIN-4 BUT NOT AFTER TREATMENT WITH SPECIFIC ANTIGEN UNLESS A SURFACE-IMMUNOGLOBULIN THRESHOLD IS EXCEEDED

Susceptibility to Fas-mediated apoptosis in nontolerant B cells is reg ulated in a receptor-specific fashion. To explore the regulation of Fa s killing in tolerant, autoreactive B cells, mice doubly transgenic fo r hen egg lysozyme (HEL)-specific B cell receptors and soluble HEL wer e examined. Engagement of CD40 led to enhanced Fas expression and acqu isition of sensitivity to Fas-mediated apoptosis in tolerant B cells, similar to that observed in nontolerant, receptor transgenic B cells. Engagement of surface immunoglobulin by specific (HEL) antigen failed to induce Fas resistance in tolerant B cells, in contrast to its effec t on nontolerant B cells; however, cross-linking of biotinylated HEL w ith streptavidin induced similar levels of Fas resistance in tolerant and nontolerant B cells, which approximated the degree of Fas resistan ce produced by anti-Ig. Unlike surface Ig (sig) engagement, physiologi cal engagement of IL-4 receptors produced similar levels of Fas resist ance in tolerant and nontolerant B cells. Thus, tolerant B cells diffe r from nontolerant B cells in the diminished capacity of surface immun oglobulin engagement to produce Fas resistance; however, tolerant B ce lls can be induced to become resistant to Fas-mediated apoptosis by IL -4 or by higher order cross-linking of sIg receptors.