Extrafollicular foci-derived B cells provide long-lived mucosal immunity (84.16)

Abstract

Abstract Antibodies to influenza are contributed by extrafollicular foci and germinal centers. The latter induce long-lived immunity via bone marrow plasma cells and memory B cells. Extrafollicular foci are thought to only provide early, short-lived responses generated from high-affinity B cells. The selection of the highest affine B cells into the early response might ensure survival from acute infection, but it seems counterintuitive that they would be excluded from the long-lived response. Here we assessed the contributions of the extrafollicular foci response to long-term immunity. We tracked a prototypic early B cell response to hemagglutinin (HA) of influenza A/PR8 in BALB/c mice by multicolor flow cytometry using an idiotype-specific mAb to the C12 idiotype (Id) together with fluorescent-labeled HA. C12Id+ HA-specific antibodies were measured by ELISA and ELISPOT. The results demonstrate the extrafollicular nature of the C12Id response and the lack of C12Id+ bone marrow plasma cells. Nonetheless, following infection HA-specific serum C12Id+ antibodies were measurable for the life of mice, secreted presumably by antibody-secreting C12Id+ plasma cells present in the lung. BrDU-labeling experiments suggested continuous turnover of these cells. Thus, extrafollicular foci induce long-term mucosal antibody responses via short-lived plasma cells. Supported by NIH AI051354 (N.B) and T32 HL007013 (K.R.).