Objective : The link between infection and autoimmunity is yet not well understood. This study was designed to evaluate if an acute viral infection known to induce type I interferon production, like influenza, can, by itself, be responsible for the breakdown of immune tolerance and for autoimmunity. Methods : We first tested the effects of influenza virus on B cells in vitro. We, then, infected different transgenic mice expressing human Rheumatoid Factors (RF) in the absence or in the constitutive presence of the autoantigen (human IgG) and young lupus prone mice (NZB/NZW F1) with influenza virus and looked for B cell activation. Results : In vitro, the virus induces B cell activation through type I interferon production by non B cells, but does not directly stimulate purified B cells. In vivo, both RF and non-RF B cells were activated in an autoantigen-independent manner. This activation was abortive since IgM and IgM-RF productions were not increased in infected mice compared to uninfected controls, whether or not anti influenza human IgG were detected, and even after viral rechallenge. As in RF tg mice, acute viral infection of NZB/NZW F1 mice induced only an abortive activation of B cells, and no increase in autoantibody production compared to uninfected animals. Conclusion : Taken together, these experiments show that virus induced acute type I interferon production is not able by itself to break down B cell tolerance in both normal and autoimmune genetic backgrounds.