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Transnuclear mice are generated from B cells with a receptor specific for the haemagglutinin of influenza A virus; the authors show that influenza virus can infect and deplete haemagglutinin-specific B cells in the lung, which might confer a replicative advantage to the virus and allow it to evade an early neutralizing response. Flu virus negates early host response Using FluBI mice, a transgenic system containing B cells with a cellular receptor specific for the HA antigen of influenza, Hidde Ploegh and colleagues show that influenza virus can infect and deplete HA-specific B cells in the lung. The authors speculate that by targeting and killing influenza-specific B cells, the virus may gain a replicative advantage sufficient for it to evade an early neutralizing response and to become established in the lung. Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection 1 . However, the outcome of interactions between an influenza haemagglutinin-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer we generated mice that harbour B cells with a BCR specific for the haemagglutinin of influenza A/WSN/33 virus (FluBI mice). Their B cells secrete an immunoglobulin gamma 2b that neutralizes infectious virus. Whereas B cells from FluBI and control mice bind equivalent amounts of virus through interaction of haemagglutinin with surface-disposed sialic acids, the A/WSN/33 virus infects only the haemagglutinin-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with haemagglutinin, causing both disruption of antibody secretion and FluBI B-cell death within 18 h. In mice infected with A/WSN/33, lung-resident FluBI B cells are infected by the virus, thus delaying the onset of protective antibody release into the lungs, whereas FluBI cells in the draining lymph node are not infected and proliferate. We propose that influenza targets and kills influenza-specific B cells in the lung, thus allowing the virus to gain purchase before the initiation of an effective adaptive response.

Short viral antigens bound to human major histocompatibility complex (HLA) class I molecules are presented on infected cells. Vaccine development frequently relies on synthetic peptides to identify optimal HLA class I ligands. However, when natural peptides are analyzed, more complex mixtures are found. By immunoproteomics analysis, we identify in this study a physiologically processed HLA ligand derived from the human respiratory syncytial virus matrix protein that is very different from what was expected from studies with synthetic peptides. This natural HLA‐Cw4 class I ligand uses alternative interactions to the anchor motifs previously described for its presenting HLA‐Cw4 class I molecule. Finally, this octameric peptide shares its C‐terminal core with the H‐2Db nonamer ligand previously identified in the mouse model. These data have implications for the identification of antiviral cytotoxic T lymphocyte responses and for vaccine development.