Final Report Summary - MEMO-B (The B cell memory program: cell fate determinants and functional diversity of B cell subsets)
B cells are key actors of successful vaccines and, until recently, the distinct effector functions of the different subsets mobilized during an immune response have been largely overlooked. We have developed a mouse reporter line allowing us to follow the fate of memory subsets upon successive immune challenges, and shown the differential impact of persistent antigen reactive structures and serum immunoglobulin levels on the differentiation of memory B cells upon a new challenge, differentiation towards either antibody secretion or new rounds of improvement of antigen recognition (affinity maturation).This model have also revealed an important systemic memory compartment triggered by the gut flora, indicating that commensal bacteria shape not only the mucosal immune response, but also major populations of memory and antibody-secreting cells in peripheral lymphoid organs and bone marrow.
Encapsulated bacteria, like Streptococcus pneumoniae and Neisseiria meningitidis, represent a threat for children health, notably in underdeveloped countries, and for the elderly. We have comforted the proposition of a specialized B subset involved in the response to such antigens in humans with distinct activation and repertoire characteristics, a first step towards a better design of conditions allowing its specific mobilization. Lastly, unanticipated processes of plasma cell persistence accounting for the somewhat disappointing outcome of B-cell depletion therapies in antibody-mediated autoimmune diseases have been described, an observation which suggests new therapeutic antibody combinations for a better elimination of pathogenic antibody-secreting cells, and may have wide relevance for such diseases, notably for lupus.
Encapsulated bacteria, like Streptococcus pneumoniae and Neisseiria meningitidis, represent a threat for children health, notably in underdeveloped countries, and for the elderly. We have comforted the proposition of a specialized B subset involved in the response to such antigens in humans with distinct activation and repertoire characteristics, a first step towards a better design of conditions allowing its specific mobilization. Lastly, unanticipated processes of plasma cell persistence accounting for the somewhat disappointing outcome of B-cell depletion therapies in antibody-mediated autoimmune diseases have been described, an observation which suggests new therapeutic antibody combinations for a better elimination of pathogenic antibody-secreting cells, and may have wide relevance for such diseases, notably for lupus.