T-bet+ Memory B-Cells Link to Local Cross Reactive IgG Upon Human Rhinovirus Infection

Human rhinoviruses cause the common cold, and exacerbate chronic respiratory diseases. Although infection elicits neutralizing antibodies, these do not persist or cross protect across multiple rhinovirus strains. To analyze rhinovirus specific B cell responses in man, we developed techniques using intact RV A16 and RV A39 for high throughput high dimensional single cell analysis, with parallel assessment of antibody isotypes in an experimental infection model. Our approach identified T bet+ B cells binding both viruses that account for ~5% of CXCR5- memory B cells. These B-cells infiltrate nasal tissue and expand in the blood after infection. Moreover, their rapid secretion of heterotypic IgG, but not IgA in vitro, matches the nasal antibody profile post-infection. By contrast, CXCR5+ memory B cells binding a single virus are clonally distinct, absent in nasal tissue, and secrete homotypic IgG and IgA mirroring the systemic response. The temporal and spatial functions of dichotomous memory B cells might explain the ability to resolve infection while rendering the host susceptible to re infection.