To B or Not to B: Understanding B Cell Responses in the Development of Malaria Infection

Abstract

Malaria is a widespread disease caused mainly by the Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) protozoan parasites. Depending on the parasite responsible for the infection, high morbidity and mortality can be triggered. To escape the host immune responses, Plasmodium parasites disturb the functionality of B cell subsets among other cell types. However, some antibodies elicited during a malaria infection have the potential to block pathogen invasion and dissemination into the host. Thus, the question remains, why is protection not developed and maintained after the primary parasite exposure? In this review, we discuss different aspects of B cell responses against Plasmodium antigens during malaria infection. Since most studies have focused on the quantification of serum antibody titers, those B cell responses have not been fully characterized. However, to secrete antibodies, a complex cellular response is set up, including not only the activation and differentiation of B cells into antibody-secreting cells, but also the participation of other cell subsets in the germinal center reactions. Therefore, a better understanding of how B cell subsets are stimulated during malaria infection will provide essential insights toward the design of potent interventions.

Keywords: B cell biology; antibodies; effective mechanism; malaria; protective immunity.

Figure 1

B cell response triggered by malaria infection. (A) During a malaria infection, the naive B cells are activated by a Plasmodium antigen through the interaction with B cell receptors (BCR), leading to their differentiation into marginal zone B cells (MZB), follicular B cells (FoB), or unswitched memory B cell (MBCs). The switched and atypical MBCs are derived from the activation of FoBs within the germinal centers (GCs). Either the MZBs, or the unswitched, switched, or atypical MBCs can differentiate into antibody-secreting cells (ASCs). These ASCs range from short-lived, low-affinity, IgM+ to long-lived, high-affinity, IgM+ or IgG+. This variation depends on the type of interaction between a particular B cell with a T cell subset. The activated Th1 T cells migrate to the GCs, becoming follicular T helper cells (TFh) that help the GC reactions (acquisition of somatic hypermutations in V(D)J Ig genes and class switch by activated FoBs). Contrarily, the regulatory T cells (Tregs) have the potential to inhibit TFh cell differentiation and GC reactions. (B) A single parasite infection can induce the differentiation of multiple Plasmodium-specific B cell clones. However, the repeated parasite exposures shift the MBC frequencies with an increase for an atypical MBC over the unswitched or switched MBCs. This shift in cell frequency may interfere on the function of the secreted antibodies and, consequently, on the development of protective immunity.