LP-BM5 Retrovirus-Expanded Monocytic Myeloid-Derived Suppressor Cells Alter B Cell Phenotype and Function.

Abstract

Our laboratory demonstrated that infection with the murine retrovirus LP-BM5 results in increased numbers of monocytic myeloid-derived suppressor cells (M-MDSCs) and that these M-MDSCs suppress not only T but also B cell responses. Because of the paucity of studies regarding the effects of MDSCs in general on B cells, we focused on these understudied B cell targets for M-MDSC effects on B cell phenotypic and functional parameters. M-MDSCs specifically decreased the proliferation of transitional type 2 (T2) B cells in response to polyclonal stimulation but increased germinal center and Ab-secreting B cell proportions and class-switched Ig production. Additionally, M-MDSCs inhibited the expression of CD40 and MHC class II on stimulated B cells and suppressed Ag presentation to Ag-specific CD4+ T cells. These alterations of the B cell compartment coincided with decreases in aerobic glycolysis, mitochondrial respiration, and glucose consumption; the latter specifically decreased in the T2 subset. To compare B cell targets of ex vivo M-MDSC suppression with the status of B cells during the course of LP-BM5-induced pathogenesis, including immunodeficiency in vivo, B cells from LP-BM5-infected mice were collected and analyzed. LP-BM5 infection resulted in several analogous alterations of B cells, as were observed with retrovirally expanded M-MDSC suppression in vitro, including decreased proliferation of T2 B cells, an increased proportion of germinal center and Ab-secreting B cells, increased production of class-switched Abs, decreased expression of CD40, and decreased metabolic activity upon stimulation.