CD4+ T lymphocytes play a central role in antibody responses to T cell dependent antigens by activating B lymphocytes, promoting their survival and allowing affinity maturation and isotype switch. CD4+ T cells also control cell-mediated immune responses as well as allergic reactions. It is still unclear whether CD4+ T lymphocytes helping B cells represent a specialised sub-population or if they belong to a larger population having multiple functions. Recent data from the literature and vaccination studies suggest that CD4+ T cell-dependent antibody secretion by B lymphocytes could be dissociated from production of Th1 and Th2 cytokines. The aim of our project is to identify and characterize CD4+ T lymphocytes specialised in helping antibody production by B lymphocytes. As T helper cell for antibody secretion cannot be distinguished from naive T cells on a cytokine production-base data, we developed an in vitro test to directly detect their capacity to sustain an IgG class switch in B cell cooperation tests. This experimental setting allowed us to compare the B cell help activity mediated by distinct CD4+ T cell populations obtained following antigen inoculation in transgenic mice. Our results suggest that B helper T cells differ from both Th1 and Th2 cells and could therefore represent a 'new' CD4+ T cell population (ThB) distinct from the 'classical' Th1 and Th2 cytokine producer cells. In vivo induction of ThB function (leading to an optimal humoral response) in the absence of a cytokine-mediated inflammatory response could be of great potential in the development of vaccine strategies. We therefore studied the ThB cell activation requirements following a dendritic cell (DC)-based immunisation protocol in mice. Interestingly, we observed that DC kept in an 'immature' state were fully capable of promoting antigen specific antibody secretion in vivo, despite defective IFN induction. Eperiments are under way to assess the role of various factors (cytokines, transcription factors,') in the differentiation of naïve T cells towards the ThB cell type. These studies may lead to novel vaccination strategies inducing optimal antibody responses while minimizing local inflammatory reactions. [CD4+ T lymphocytes play a central role in antibody responses to T cell dependent antigens by activating B lymphocytes, promoting their survival and allowing affinity maturation and isotype switch. CD4+ T cells also control cell-mediated immune responses as well as allergic reactions. It is still unclear whether CD4+ T lymphocytes helping B cells represent a specialised sub-population or if they belong to a larger population having multiple functions. Recent data from the literature and vaccination studies suggest that CD4+ T cell-dependent antibody secretion by B lymphocytes could be dissociated from production of Th1 and Th2 cytokines. The aim of our project is to identify and characterize CD4+ T lymphocytes specialised in helping antibody production by B lymphocytes. As T helper cell for antibody secretion cannot be distinguished from naive T cells on a cytokine production-base data, we developed an in vitro test to directly detect their capacity to sustain an IgG class switch in B cell cooperation tests. This experimental setting allowed us to compare the B cell help activity mediated by distinct CD4+ T cell populations obtained following antigen inoculation in transgenic mice. Our results suggest that B helper T cells differ from both Th1 and Th2 cells and could therefore represent a 'new' CD4+ T cell population (ThB) distinct from the 'classical' Th1 and Th2 cytokine producer cells. In vivo induction of ThB function (leading to an optimal humoral response) in the absence of a cytokine-mediated inflammatory response could be of great potential in the development of vaccine strategies. We therefore studied the ThB cell activation requirements following a dendritic cell (DC)-based immunisation protocol in mice. Interestingly, we observed that DC kept in an 'immature' state were fully capable of promoting antigen specific antibody secretion in vivo, despite defective IFN induction. Experiments are under way to assess the role of various factors (cytokines, transcription factors,') in the differentiation of naïve T cells towards the ThB cell type. These studies may lead to novel vaccination strategies inducing optimal antibody responses while minimizing local inflammatory reactions.]