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 mol ecules 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 a ny, in the development of CD4 memory is unknown. We compared responses of C D4 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 a bsence 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 c ells did not affect the survival of memory CD4 cells since frequencies rema ined stable, Despite normal dendritic cell function, multiple immunizations of B cell-deficient mice did not restore frequencies of memory cells. Howe ver, the transfer of B cells restored memory cell development, Ag presentat ion was not essential since B cells activated in vitro with irrelevant Ag a lso restored frequencies of memory cells, The results provide unequivocal e vidence that B cells play a critical role in regulating clonal expansion of CD I cells and, as such, are requisite for the optimal priming of memory i n the CD4 population.