Antigen-specific B cell receptor sensitizes B cells to infection by influenza virus

Influenza A virus-specific B lymphocytes and the antibodies they produce protect against infection (1). However, the outcome of interactions between a flu hemagglutinin (HA)-specific B cell via its receptor (BCR) and virus is unclear. Through somatic cell nuclear transfer (SCNT) we generated mice that harbor B cells with a BCR specific for the HA of A/WSN/33 (FluBI mice). Their B cells secrete an IgG2b that neutralizes infectious virus. While B cells from FluBI and control mice bind equivalent amounts of virus through interactions of HA with surface-disposed sialic acids, the A/WSN/33 virus infects only the HA-specific B cells. Mere binding of virus is not sufficient for infection of B cells: this requires interactions of the BCR with HA, causing both disruption of antibody secretion and FluBI B cell death within 18 hours. 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, while 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 prior to the initiation of an effective adaptive response.