Artemisinin attenuates IgM xenoantibody production via inhibition of T cell-independent marginal zone B cell proliferation

Abstract

Artemisinin (ART) has been shown to suppress B cell activation and plasma cell formation. However, its effect on splenic marginal zone (MZ) B cells is unknown. Splenic MZ B cells play a critical role in rapidly induced Ab production against blood-borne foreign Ags. Dysfunction of MZ B cells, due to inhibition of its proliferation or displacement of its homing, results in an attenuated adaptive humoral response. Here, we investigate the effect of ART on splenic MZ B (CD19⁺ CD21^high CD23^low ) and B10 (CD19⁺ CD1d^high CD5⁺ ) B cells to explore the mechanisms of ART-induced immunosuppression in T cell-deficient nude mice challenged with hamster xenoantigens. In this study, we demonstrate that ART decreases T cell-independent xenogeneic IgM Ab production and, this is associated with a strong suppression of MZ B cell proliferation and a relative increase of CD21^low CD23⁺ follicular and B10 B cells. In addition, this suppression impairs IL-10 production. Taken together, our data indicate that ART suppresses B cell immune responses through a distinctive effect on splenic MZ B and other B cells. This represents a new mechanism of ART-induced immunosuppression.

Keywords: IL-10; humoral immunity; immunization; marginal zone; murine model; regulatory B cells.