The precise number and nature of signaling events required for T helper cell dependent activation of quiescent B lymphocytes remains obscure. Here we discuss the extant literature, as well as recent unpublished findings from our own laboratory, which address the issue. Based on available information, we suggest that activation of quiescent B cells into proliferative cycle requires signaling mediated by antigen, IL4 and T cell associated by alphabetaTCR and CD4 and transduced through B cell membrane immunoglobulins, IL4 receptors and Ia respectively. Further, these signals must be received in sequence and are transduced by distinct biochemical mechanisms.