Abstract
Antibodies have long been shown to play a critical role in naturally acquired immunity to malaria, but it has been suggested that Plasmodium-specific antibodies in humans may not be long lived. The cellular mechanisms underlying B cell and antibody responses are difficult to study in human infections; therefore, we have investigated the kinetics, duration and characteristics of the Plasmodium-specific memory B cell response in an infection of P. chabaudi in mice. Memory B cells and plasma cells specific for the C-terminal region of Merozoite Surface Protein 1 were detectable for more than eight months following primary infection. Furthermore, a classical memory response comprised predominantly of the T-cell dependent isotypes IgG2c, IgG2b and IgG1 was elicited upon rechallenge with the homologous parasite, confirming the generation of functional memory B cells. Using cyclophosphamide treatment to discriminate between long-lived and short-lived plasma cells, we demonstrated long-lived cells secreting Plasmodium-specific IgG in both bone marrow and in spleens of infected mice. The presence of these long-lived cells was independent of the presence of chronic infection, as removal of parasites with anti-malarial drugs had no impact on their numbers. Thus, in this model of malaria, both functional Plasmodium-specific memory B cells and long-lived plasma cells can be generated, suggesting that defects in generating these cell populations may not be the reason for generating short-lived antibody responses.
Highlights
There is longstanding evidence that naturally acquired immunity to the erythrocytic stages of malaria is strongly dependent on antibodies (Abs) [1,2,3,4,5,6]
MSP119-specific immunoglobulin G (IgG) memory B and antibody secreting cells are detectable for up to 8 months following a primary infection We examined whether MSP119-specific Ab secreting cells (ASC)
The numbers of MSP119-specific IgG ASC in the bone marrow and spleen were strongly correlated with the concentrations of MSP119-specific IgG in plasma (Supplementary Figure S1), suggesting that concentrations of plasma Ab can be a good surrogate for ASC (Plasma cells) in the bone-marrow
Summary
There is longstanding evidence that naturally acquired immunity to the erythrocytic stages of malaria is strongly dependent on antibodies (Abs) [1,2,3,4,5,6]. Acquisition of immunity to P. falciparum malaria in humans is a relatively inefficient process; slow to develop, never sterile and wanes quickly in the absence of continued exposure to infection [7,8,9] This would suggest that intermittent exposure to parasite antigens is required, at least for several years, for maintenance of both the memory and effector arms of the immune response to P. falciparum. The biological explanation for this apparent dependence of naturally acquired immunity to continued antigen exposure in residents of malaria endemic areas is still a subject of debate During both experimental and human malaria, there is evidence for loss of memory or activated CD4+ T cells, B cells and plasma cells and short-lived malaria specific Abs after a primary acute infection [10,11,12,13], suggesting that some of the components contributing to the humoral response may be shortlived. There are conflicting reports on the longevity of Ab reponses to Plasmodium; in some longitudinal studies [14,15,16], short-lived Ab responses with reduced half lives [17] have been reported, whereas other studies report that Ab responses persist [18,19] and are protective [5], and it has yet to be settled whether there are any deficiencies in the generation and maintenance of Plasmodium-specific memory B cells and Abs
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