EVIDENCE FOR A CRITICAL ROLE FOR IL-2 IN CD40-MEDIATED ACTIVATION OF NAIVE B-CELLS BY PRIMARY CD4 T-CELLS

The interaction of CD40 on B cells with the CD40 ligand (CD40L) on pre activated CD4 T cells is critical for the initiation of T-dependent Ab responses. It is believed that signals via CD40 synergize with cytoki nes (e.g., IL-4 and IL-5) to drive B cell activation. However, primary T cells preactivated via CD3 alone cannot induce B cell proliferation ; we have shown previously that costimulation of T cells via CD3 and C D28 stabilizes the expression of the CD40L, which we propose contribut es to their capacity to act as competent helper-effector cells. Here w e show that an additional, critical reason why CD3-stimulated CD40L-be aring T cells are incompetent helper cells is because they secrete ins ufficient IL-2. In contrast, CD28/CD3-activated T cells induce a cells to become IL-2 responsive via a combination of CD40L and IL-2-mediate d signals, and these two stimuli subsequently drive B cell proliferati on and IgM secretion. We therefore propose that T cells must first enc ounter Al: in conjunction with CD80/86 on APCs, This leads to the stab le expression of CD40L and maximal secretion of IL-2, which together r ender primary T cells competent to activate B cells in an IL-2-depende nt fashion.