Strength of signal through BCR determines the fate of cycling B cells by regulating the expression of the Bcl-2 family of survival proteins

Cycling, splenic B cells were recultured with: (1) no stimulant to reflect poorly competitive clones; (2) soluble, whole anti-μ to reflect clones that bind soluble immune complexes; (3) soluble F(ab')₂ anti-μ to reflect clones that bind soluble antigen; and (4) immobilized anti-μ to reflect clones that bind antigen presented by FDC. All four groups displayed similar levels of the death proteins Bax and Bcl-x(s). In contrast, cycling B cells restimulated with either soluble F(ab')₂ or immobilized anti-μ expressed heightened levels of the survival protein Bcl-X(L), and only cells restimulated with immobilized anti-μ expressed the survival protein Bcl-2. Cycling B cells restimulated with either soluble F(ab')₂ or immobilized anti-μ displayed a selective survival advantage over cycling B cells receiving no stimulus or soluble, whole anti-μ by both enhancing their responsiveness to CD40 ligand, a Th-cell-derived signal, and increasing the period that the cycling B cells remained responsive to this Th-cell-derived signal. The Th-cell-derived signal did not appreciably alter cycling B cell expression of Bcl-2 family members.