B-cell memory in malaria: Myths and realities

Abstract

B-cell and antibody responses to Plasmodium spp., the parasite that causes malaria, are critical for control of parasitemia and associated immunopathology. Antibodies also provide protection to reinfection. Long-lasting B-cell memory has been shown to occur in response to Plasmodium spp. in experimental model infections, and in human malaria. However, there are reports that antibody responses to several malaria antigens in young children living with malaria are not similarly long-lived, suggesting a dysfunction in the maintenance of circulating antibodies. Some studies attribute this to the expansion of atypical memory B cells (AMB), which express multiple inhibitory receptors and activation markers, and are hyporesponsive to B-cell receptor (BCR) restimulation in vitro. AMB are also expanded in other chronic infections such as tuberculosis, hepatitis B and C, and HIV, as well as in autoimmunity and old age, highlighting the importance of understanding their role in immunity. Whether AMB are dysfunctional remains controversial, as there are also studies in other infections showing that AMB can produce isotype-switched antibodies and in mouse can contribute to protection against infection. In light of these controversies, we review the most recent literature on either side of the debate and challenge some of the currently held views regarding B-cell responses to Plasmodium infections.

Keywords: Plasmodium; classical and atypical memory B cells; long-lived plasma cells; malaria.

Figure 1

Pathogen‐specific B‐cell responses. (A) Schematic representation of the germinal center (GC) B‐cell response, which results in the generation of two arms of B‐cell memory, long‐lived plasma cells and memory B cells. (B) Schematic representation of the kinetics of B‐cell responses to pathogens, showing the expansion/activation phase (1), the contraction phase (2), and the memory phase (3). FDC: follicular dendritic cell; Tfh: follicular helper T cell

Figure 2

Plasmodium infection. (A) Schematic representation of pre‐erythrocytic (liver) and erythrocytic (blood) stages of Plasmodium spp. infection in the mammalian host. (B) Schematic representation of the course of erythrocytic P. chabaudi infection in C57BL/6 mice

Figure 3

Signals known or suggested to support the generation of either classical or atypical memory B cells in response to Plasmodium spp. infection. SAP: signaling lymphocyte activation molecule (SLAM)‐associated protein; ICOS: inducible T cell co‐stimulator; cGAS: pattern recognition receptor cyclic GMP‐AMP synthase; TLR: toll‐like receptor