A 39-KDA PROTEIN ON ACTIVATED HELPER T-CELLS BINDS CD40 AND TRANSDUCES THE SIGNAL FOR COGNATE ACTIVATION OF B-CELLS

CD40 is a B-cell surface molecule that has been shown to induce B-cell growth upon ligation with monoclonal antibodies. This report shows that triggering via CD40 is essential for the activation of resting B cells by helper T cells (T(h)). A soluble fusion protein of CD40 and human immunoglobulin, CD40-Ig, inhibited the induction of B-cell cycle entry, proliferation, and differentiation by activated T(h)1 and T(h)2. The ligand for CD40 was identified as a 39-kDa membrane protein that was selectively expressed on activated T(h). A monoclonal antibody specific for the 39-kDa protein inhibited CD40-Ig binding and also inhibited the activation of B cells by T(h). These data indicate that the 39-kDa membrane protein expressed on activated T(h) is a binding protein for CD40 and functions to transduce the signal for T(h)-dependent B-cell activation.