T cell stimulation of B cell proliferation during T‐B collaboration requires membrane‐bound stimulatory ligands, such as CD40 ligand and the secretion of soluble cytokines, such as IL‐4. Nevertheless, it remains unclear whether T cell contact is required to provoke each consecutive B cell division, or whether B cells divide in a T cell‐free burst following the initial stimulation. To test this, naive B cells were cultured with anti‐CD40 monoclonal antibody (mAb) and IL‐4 and, after various times, these stimuli were removed and the cells re‐cultured with or without further stimulation. Following stimulus removal, B cells were able to continue proliferating, with the size of the B cell burst dependent on the strength of the initial anti‐CD40 mAb stimulus. Furthermore, in the absence of activating signals from anti‐CD40 and/or IL‐4, re‐cultured B cells died rapidly. In addition, B cells undergoing a stimulus‐free division burst could switch to IgG1. Thus, maximal B cell proliferation, differentiation and survival may require continued, although not necessarily consecutive, cognate interactions with T cells. These results suggest that antigen persistence and T cell help are necessary to sustain B cell proliferation and differentiation in vivo.