Follicular dendritic cells in vitro modulate the expression of Fas and Bcl-2 on germinal center B cells

Abstract.

Germinal center (GC) B cells are highly susceptible to apoptosis. The cellular mechanism regulating this sensitivity, however, has not yet been fully delineated. To investigate whether follicular dendritic cells (FDC) are capable of regulating the susceptibility to apoptosis of GC B cells, we constructed a GC model in vitro: emperipolesis of tonsillar B cells by FDC. We then analyzed the expressions of apoptosis-related proteins (Bcl-2 and Fas) on the cells by three-color flow cytometry. B cells nonentrapped by FDC decreased rapidly in number owing to early apoptosis in vitro, whereas entrapped B cells were rescued for at least 18 h and showed peculiar regulation of Fas and Bcl-2. GC founder cells (CD38⁺, IgD⁺; GCFC) and GC B cells (CD38⁺, IgD^–) showed approximately a twofold increased expression of Fas; in contrast, mantle zone B cells (CD38^–, IgD⁺) and memory B cells (CD38^–, IgD^–) showed no changes. Bcl-2 expression in mantle zone and memory B cells was reduced by approximately one-half; however, GCFC and GC B cells continued to express little Bcl-2 and this did not change. Our findings strongly suggest that FDC play a part in the modulation of the susceptibility to apoptosis on B cells within GC.