Immunosenescence is characterized by an increase in autoantibody production. Because both T and B cell stimulation are key events for producing antibodies, we investigated early T and B cell activation by means of CD23 and CD40L (two very early activation antigens). PBMC from elderly humans (EH) were studied following culture with either medium, anti-CD3mAb, rIL-4, or PMA + ionomycin. CD23 expression on elderly B cells after anti-CD3 challenge of PBMC, a reflect of T-dependent B cell activation, was clearly defective. Conversely, CD23 expression on EH B cells following activation with soluble factors as rIL-4 was preserved. CD40L expression was also impaired in EH T cells following anti-CD3 challenge. However, activation by means of PMA and/or ionomycin was preserved both in T cells (CD40L expression) and in B cells (CD23 expression). These results indicate that a defective T-dependent B cell activation related to defective T cell activation located between surface membrane and PKC/ionomycin function is an intrinsic characteristic of immunosenescence. We have not found intrinsic B-cell defects, and we conclude that the characteristically impaired early B cell activation in EH is mostly due to T cell defects.