Patients suffering from rheumatoid arthritis are frequently treated with the monoclonal anti-CD20 antibody Rituximab®, which efficiently depletes recirculating B cells. As a consequence, those patients do not mount sufficient antibody responses to protect against pathogenic infections and need to be vaccinated against several pathogens prior to treatment. Seasonal influenza vaccines often are only available when patients already started Rituximab®-treatment. Nevertheless, those patients profit of influenza-vaccination, probably due to the induction of protective T cell responses.
Here we studied the effect of B cell responses on virus-specific CD8+ T cell responses in mice and Rituximab®-treated patients. B cell-deficient JHT mice infected with mouse-adapted influenza virus (strain PR8) showed a dramatically reduced expansion of influenza-specific CD8+ T cells compared with wild type mice. Of note, JHT mice have no intrinsic impairment of CD8+ T cell expansion since they mount normal T cell responses upon vaccinia virus (VACV)-infection. Thus, B cells are capable of modulating CD8+ T cell responses depending on properties of the pathogen. Interestingly, patients treated with Rituximab® showed severely reduced expansion of influenza-specific CD8+ T cells after Influvac®-vaccination. Therefore, Rituximab®-treatment causes not only a reduction of humoral immunity but moreover affects the cellular response of cytotoxic T cells. Most interestingly, the underlying mechanism of how B cells influence CD8+ responses is dependent on functional type I interferon receptor (IFNAR)-signaling of B cells. This was demonstrated by conditional mice with a B-cell selective IFNAR-deficiency (CD19Cre+/-IFNARflox/flox), which showed reduced CD8+ T cell expansion as similarly detected in B cell-deficient mice. In conclusion, the choice of an appropriate vaccine to treat B cell-deleted patients has to be reevaluated in order to efficiently induce protective CD8+ T cell responses.