After germinal center B cells undergo somatic mutation and antigen sel
ection, they become either memory B cells or plasma cells, but the sig
nal requirements that control entry into either pathway have been uncl
ear. When purified human germinal center cells were cultured with inte
rleukin-2, interleukin-10, and cells expressing CD40 ligand, cells wit
h characteristics of memory B cells were generated. Removal of CD40 li
gand from the system resulted in terminal differentiation of germinal
center B cells into cells with the characteristics of plasma cells. Th
ese results indicate that CD40 ligand directs the differentiation of g
erminal center B cells toward memory B cells rather than toward plasma
cells.