The ability of B cells to participate in allogeneic cognate T-B cell interactions in vitro depends on the presence of CD4+ T cells during their development.

We have assessed in vitro whether the absence of T cells in the natural environment of F1 hybrid mice influences the ability of their B cells to participate in an allogeneic interaction with CD4+ cells from parental mice. For this purpose, B cells from athymic CB6F1 nu/nu mice or from CB6F1 mice depleted in different T cell subsets were incubated in vitro with purified CD4+ BALB/c cells. Here, we show that B cells from CB6F1 nu/nu mice or from euthymic CB6F1 mice depleted from birth of CD4+ cells were unable to respond to allogeneic stimulation with BALB/c CD4+ T cells, which produce normal levels of cytokines. The addition of dendritic cells from euthymic CB6F1 mice did not revert this defect. B cells from CB6F1 mice lacking CD4+ T cells showed a selective reduction in the expression of CD23. We found a complete restoration of both the CD23 expression and the ability of CB6F1 nu/nu B cells to respond in vitro to an allogeneic stimulation by CD4+ cells in two instances: (1) after neonatal engraftment of a syngeneic thymus into CB6F1 nu/nu mice, which partially reconstitutes the mature T cell populations; and (2) after preincubation of B cells from CB6F1 nu/nu mice with high concentrations of rIL-4. However, the addition of an anti-CD23 mAb did not interfere with the polyclonal activation of CB6F1 B cells in this system. These results indicate that CD4+ cells play an important role in the functional maturation of B cells by promoting their ability to participate in allogeneic cognate T-B cell interactions.