The functional role of B cell antigen receptor stimulation and IL-4 in the generation of human memory B cells from germinal center B cells.

The germinal center (GC) is an anatomical site where memory B cells are generated. Ag-Ab complexes presented by follicular dendritic cells in GC select precursors of memory B cells. Using a unique in vitro experimental system in which the survival of GC B cells is supported by a defined follicular dendritic cell-like cell line, we investigated the effects of B cell Ag receptor (BCR) stimulation and IL-4 on the memory B cell generation from centroblasts. IL-4 is reported to be critical for GC formation. Centroblasts differentiated to centrocytes during the culture period of 3 days as demonstrated by the down-regulation of CD77 expression and induction of CD44 as well as Bcl-2 expression. The transition of centroblast to centrocyte was enhanced by BCR stimulation and IL-4. Upon further culture, the centrocytes differentiated to memory B cells, a process that was enhanced by BCR stimulation and IL-4. The presence of IL-4 in the culture did not increase the number of plasma cells. These experimental data provide formal in vitro evidence that Ags in GC may participate not only in the selection but also in the expansion of memory B cells and that IL-4 is a growth factor promoting this expansion.