Acute Disruption of Bone Marrow B Lymphopoiesis and Apoptosis of Transitional and Marginal Zone B Cells in the Spleen following a Blood-Stage Plasmodium chabaudi Infection in Mice
B cells and antibodies are essential for the protective immune response against a blood-stage Plasmodium infection. Although extensive research has focused on memory as well as plasma B-cell responses during infection, little is known about how malaria affects B-cell development and splenic maturation into marginal zone B (MZB) and follicular B (FoB) cells. In this study, we show that acute Plasmodium chabaudi AS infection in C57Bl/6 mice causes severe disruption of B lymphopoiesis in the bone marrow, affecting in particular pro-, pre-, and immature B cells as well as the expression of the bone marrow B-cell retention chemokine CXCL12. In addition, elevated apoptosis of transitional T2 and marginal zone (MZ) B cells was observed during and subsequent to the control of the first wave of parasitemia. In contrast, Folllicular (Fo) B cells levels were retained in the spleen throughout the infection, suggesting that these are essential for parasite clearance and proper infection control. 1. Introduction Malaria is a major health problem in developing countries, affecting each year at least 300–500 million individuals of which more than 1 million people die of serious complications. Primarily in children beyond 5 years, parasite-mediated processes and excessive or uncontrolled inflammation cause malaria pathogenesis, characterized by severe malarial anemia (SMA), cerebral malaria (CM), malaria-associated acute lung injury (ALI) and its more severe form malaria-associated acute respiratory distress syndrome (MA-ARDS) [1]. During a malaria infection, pre-erythrocytic liver stages are mainly attacked by CD8+ effector cells and IFN-γ, whereas antibodies are key components against the asexual blood stage of the Plasmodium life cycle [1, 2]. Studies in mice lacking B cells revealed that they were unable to clear a Plasmodium chabaudi AS (PcAS) infection and instead displayed chronic unresolved parasitemia levels for periods as long as 120 days [3]. Hence, B cells and malaria specific antibodies are, in addition to CD4+ T cells, required for effective antimalarial immunity [4–6]. Passive serum transfer studies in human corroborate these findings [7, 8]. Despite the key role of antibodies in immunity to malaria, there is a gap in our knowledge on the cellular basis of these humoral responses during infection. In malaria, several experimental studies report that a single PcAS infection induces both short-lived and long-lived plasma cells including the generation of functional memory B-cells [9–11]. In addition, some recent human malaria studies report the generation
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