Mitchell et al. showed more than 50 years ago that B cells and T cells co-operate to generate an effective immune response. In Salmonella infections, immunity is generated through CD4+ T cell responses but we and others1 have observed that B-cell deficient mice are unable to mount a protective immune response. Following recognition by cognate B cells of their antigens, CD4+ T cells activate B cells (T-dependent activation) leading to antibody production by B cells. In a co-operative process, B cells are thought to help CD4+ T cells by generating essential survival signals when antigen levels become limiting, to effect a memory phase of the immune response. This antibody independent function of B cells has not been thoroughly examined in an infectious setting. Live-attenuated vaccine (LAV) strains of Salmonella enterica serovar Typhimurium (STm) infection in susceptible C57BL/6 mice has served as an excellent model to study the adaptive immune responses. We have demonstrated that Th1 functions of the CD4+ T cells are key in the clearance of STm from the infected host2. In vaccinated animals, CD4+ T cells are also critical in the development of protective immunity. We showed that in B cell-deficient (µMT) mice, infection with LAV is cleared but these mice fail to develop protective memory. The observed phenomenon is independent of secreted antibodies as Ab-supplementation fails to rescue the protective phenotype. During the early stages of vaccination, CD4+ T cells in µMT mice exhibit apparently normal activation phenotype in terms of Th1 lineage commitment (e.g. T-bet expression) and effector function (e.g. ex-vivo IFNγ production) as compared to the wild-type C57BL/6 mice. However, T cell activation is not maintained through the later stages of vaccine clearance. The vaccinated µMT mice also show a reduction in the number of antigen-specific CD4+ T cells in the spleen; these T cells are identified with the help of STm-specific tetramers. These data demonstrate that there is a defect in the CD4+ T cell memory in the absence of B cells. Future work aims to address the mechanism by which B cells influence the development and/or maintenance of CD4+ T cell memory.