Murine norovirus inhibits B cell development in bone marrow, but does not impair antibody production in Stat1-/- mice

Abstract

Murine norovirus (MNV) is used as a model system to study human noroviruses, can infect macrophages/monocytes, neutrophils, dendritic, intestinal epithelial, T and B cells, and is highly prevalent in laboratory mice. We previously showed that MNV infection significantly reduces bone marrow B cell populations in a Stat1-dependent manner. We demonstrate here that while MNV-infected Stat1-/- mice have significant bone marrow B cell losses, expansion of splenic B cells capable of mounting an antibody response to novel antigens remains intact. We also investigated increased granulopoiesis as a mechanism of B cell loss, and we show that administration of anti-G-CSF antibody inhibits the pronounced bone marrow granulopoiesis induced by MNV infection of Stat1-/- mice, but this inhibition does not rescue bone marrow B cell losses. Therefore, these results show that MNV-infected Stat1-/- mice can still exhibit a robust humoral immune response in spite of decreased bone marrow B cells, and suggests that further investigation will be needed to identify other indirect factors or mechanisms that are responsible for the bone marrow B cell losses seen after MNV infection. Additionally, this work adds to the knowledge about the potential physiologic effects on mice with Stat1-related disruptions in research mouse colonies that may be endemically infected with MNV.