B cells are responsible for the humoral arm of the immune response and most successfulvaccines in humans are antibody-based. Depending on the pathogen, specific B cell subsets aremobilized and a variety of innate, intermediate or adaptive responses are produced. In somecases these responses generate memory in anticipation of a re-encounter with the same pathogen.B cells can also present antigens to T cells, and enhance or suppress immune responses,depending in which T cell context they are primed.The present project aims to describe new innate-like and memory B cell subsets and tounravel the molecular switch allowing the differentiation and the long-term maintenanceinto the memory program. This will be done by combining approaches in both humans andmice, in order to reveal the analogies and the differences between these two immunesystems.Our main specific aims are 1) to establish a reporter cell line that, by complementation with acDNA library from human centrocytes and memory B cells, should allow the identification of amaster gene able to trigger the memory program 2) to compare various antigenic andendogenous stimuli in terms of formation of various innate-like and memory subsets, using amouse model that, by marking irreversibly B cells during an immune response, has allowed us toreveal new layers of B-cell memory 3) to study the endogenous and exogenous signals thatsupport the development of marginal zone B cells in humans 4) to unravel the genes that governlong-term B cell memory, by isolating anti-vaccinia virus long-lived human memory B cells. Thegeneral ambition is to provide new insights into the complexity of the B cell compartment thatshould allow the improvement of B-cell targeted vaccination strategies.