Characterizations of the virus‐induced differentiation of bone marrow plasmacytoid dendritic cells into CD11b+ dendritic cells

Abstract

Plasmacytoid dendritic cells (pDCs), so called natural interferon‐producing cells (IPCs), can produce large amount of type‐I interferon (IFN‐I) upon virus infection. Intensive studies have shown that pDCs are also involved in activation and modulation of adaptive immunity. However, less is known about the regulation of their developmental plasticity during virus infection.Recently we demonstrated that bone marrow (BM) pDCs isolated from lymphocytic choriomeningitis virus (LCMV) infected mice differentiated into CD11b+ DCs in vitro. Here we provide in vivo evidence to prove the biological significance of our in vitro finding. We accomplished this by adoptive transferring pDCs isolated from LCMV infected mice and analyzing the immunoglobulin D‐J rearrangements (a genetic marker of pDCs) in CD11b+ DCs isolated from LCMV infected mice. Additionally, we demonstrated that the differentiation of pDCs into CD11b+ DCs does not rely on the infection of BM pDCs by LCMV, instead, is mediated by IFN‐I signaling. In preliminary studies we used pDC specific monoclonal antibodies against Ly49Q and Siglec‐H to characterize the pDC subtypes that differentiate into CD11b+ DCs. Collectively, our work indicates that BM pDCs constitute an important source for CD11b+ DCs during viral infection and further delineates the biological and phenotypic features of this novel DC developmental pathway.This work was supported by US. Public Health Service grant (AI 045927) and a training grant (NS041219) to L.L. from the National Institutes of Health.