It is well known that interactions between accessory molecules on T cells and their ligands on APC play a key role in regulating T cell effector activity. The factors controlling the expression of these molecules are thus important determinants in the outcome of T cell activation. We have examined the expression of the murine ligand for CD27, a costimulatory molecule on T cells. Evidence is shown that CD27L is expressed at a low level on resting B cells but not on T cells, and that activation of B cells by culture with LPS or anti-IgM Ab increases the expression of CD27L. Interestingly, coligation of CD40 down-regulates CD27L on LPS-activated B cells but not on anti-Ig-activated cells. These findings suggest that costimulation via the CD27-CD27L pathway may be limited to interactions involving Ag-specific B cells, i.e., B cells specifically activated via their Ig receptors. In addition, testing a spectrum of different cytokines indicated that IL-4 and TGF, but not IL-2, IL-10, or IFN-gamma, prevented up-regulation of CD27L expression on activated B cells even when activation was induced by Ig signaling. The capacity of IL-4 to prevent CD27L expression could thus serve to limit CD27-CD27L interactions to Th1-type T cell responses.