Title: Role of Heparan sulfate in B-cell responses

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DESCRIPTION (provided by applicant): Heparan sulfate (HS) influences many cellular processes including adhesion, motility, ligand-receptor interaction, and proliferation. We have recently observed that the expression of HS was tightly regulated on B-cells: whereas naive B-cells do not express heparan sulfate, all B-cells isolated from mice infected with viruses, or mice injected with poly I:C, express heparan sulfate. Accordingly, B-cells treated ex-vivo with IFN-I alone express high level of heparan sulfate. Our preliminary data indicates that HS expression on B-cells regulates their responsiveness to cytokines as well as their motility in vivo. Here we propose experiments aimed at validating the importance of HS for mounting of an efficient antiviral response. This work might help in the understanding of B-cell responses and has strong implication for vaccine development and autoimmunity. PUBLIC HEALTH RELEVANCE: B-cells are an essential component of our immune system. B-cell activity needs to be tightly regulated to ensure that they are properly activated during an infection (to secrete antibodies to help in the elimination of pathogens), but not in the absence o infection (to prevent autoimmunity). Our initial data indicates that upon infection, B-cells expres heparan sulfate, a sugar modification, which renders B-cells more responsive to extracellular signals and affects their ability to migrate. Here, we propose to test whether heparan sulfate expression is required for an efficient antibody response following viral infection. Our project may have implications for the development of more efficient vaccines.