A critical role for B cells in the development of memory CD4 cells

Activated B cells express high levels of class II MHC and costimulatory molecules and are nearly as effective as dendritic cells in their APC ability. Yet, their importance as APC in vivo is controversial and their role, if any, in the development of CD4 memory is unknown. We compared responses of CD4 cells from normal and B cell-deficient mice to keyhole limpet hemocyanin over 6 mo and observed diminished IL-2 production by cells primed in the absence of B cells. This was due to lower frequencies of Ag-responsive cells and not to decreased levels of IL-2 secretion per cell. The absence of B cells did not affect the survival of memory CD4 cells since frequencies remained stable. Despite normal dendritic cell function, multiple immunizations of B cell-deficient mice did not restore frequencies of memory cells. However, the transfer of B cells restored memory cell development. Ag presentation was not essential since B cells activated in vitro with irrelevant Ag also restored frequencies of memory cells. The results provide unequivocal evidence that B cells play a critical role in regulating clonal expansion of CD4 cells and, as such, are requisite for the optimal priming of memory in the CD4 population.