B‐cell fate decisions following influenza virus infection

Abstract

Rapidly induced, specific Ab generated in extrafollicular foci are important components of early immune protection to influenza virus. The signal(s) that prompt B cells to participate in extrafollicular rather than germinal center responses are incompletely understood. To study the regulation of early B‐cell differentiation events following influenza infection, we exploited earlier findings of a strong contribution of C12 idiotype‐expressing B cells to the primary HA‐specific response against influenza A/PR/8/34. Using an idiotype‐specific mAb to C12 and labeled HA, in conjunction with multicolor flow cytometry, we followed the fate of C12Id‐expressing influenza HA‐specific B cells in WT BALB/c mice, requiring neither genetic manipulation nor adoptive cell transfer. Our studies demonstrate that HA‐specific C12Id+ B cells are phenotypically indistinguishable from follicular B cells. While they induced both extrafollicular and germinal center responses, extrafollicular responses were strongly predominant. Provision of increased HA‐specific T‐cell help increased the magnitude of the extrafollicular response, but did not shift the C12Id+ response toward germinal center formation. Collectively the data are consistent with the hypothesis that B‐cell fate determination following activation is a stochastic process in which infection‐induced innate signals might drive the preferential expansion of the early extrafollicular response.