Human tonsillar subepithelial B cells, which are a marginal zone‐equivalent B cell subset, respond readily to T‐independent type 2 antigens, but not to polyclonal B cell activators in vitro. In this study, subepithelial (SE) B cells were induced to proliferate and mature into plasma cells when co‐cultured with activated T cells. The response of SE B cells was not observed when co‐cultures were carried out in transwell chambers or in the presence of blocking anti‐LFA‐1 antibodies, demonstrating the need for a close T‐B cell interaction. The presence of soluble CD40 also prevented the B cell response in vitro suggesting a pivotal role of CD40‐CD40 ligand interactions. The data are discussed in terms of the T cell dependence of marginal zone (MZ) B cell response and the possible existence of various MZ B cell subsets.