Atypical Memory B Cells Are Greatly Expanded in Individuals Living in a Malaria-Endemic Area

Abstract

Epidemiological observations in malaria endemic areas have long suggested a deficiency in the generation and maintenance of B cell memory to Plasmodium falciparum (Pf) in individuals chronically reinfected with the parasite. Recently, a functionally and phenotypically distinct population of FCRL4+ hyporesponsive memory B cells (MBCs) was reported to be expanded in HIV-infected individuals with high viral loads. In this study, we provide evidence that a phenotypically similar atypical MBC population is significantly expanded in Pf-exposed Malian adults and children as young as 2 years of age as compared with healthy U.S. adult controls. The number of these atypical MBCs was higher in children with chronic asymptomatic Pf infections compared with uninfected children, suggesting that the chronic presence of the parasite may drive expansion of these distinct MBCs. This is the first description of an atypical MBC phenotype associated with malaria. Understanding the origin and function of these MBCs could be important in informing the design of malaria vaccines.

Pregnancy and Malaria Exposure Are Associated with Changes in the B Cell Pool and in Plasma Eotaxin Levels

“…Our results add to the evidence of malaria-driven expansion of atypical MBC (21)(22)(23)(24), as shown by the consistent correlation with malaria-specific IgGs in plasma. Interestingly, in this study, to our knowledge, we show for the first time that exposure to P. vivax may drive an expansion of atypical MBC similar to P. falciparum.…”

“…However, HIV can be discarded due to its low prevalence in PNG, as follows: 0.8% in 2010 (49). Helminth infection rates are known to be high in the area (50), but acute infections do not seem to affect the levels of atypical MBC (21). In addition, a very recent manuscript demonstrated that malaria infection is followed up by an expansion of this B cell subset (24).…”

“…However, the increased levels of atypical MBC after malaria exposure might have an impact on other diseases beyond malaria due to a potential role in innate immunity. Malaria exposure induces atypical MBC to express the inhibitory receptor Fc receptor-like protein (FcRL) 4 (21,26). FcRL4 dampens BCR activation, but enhances TLR9 signaling, favoring a switch from adaptive to innate B cell signaling (51).…”

“…A population of hyporesponsive MBC characterized as CD21 low CD27 2 , called exhausted MBC, was reported to be expanded in HIV-infected individuals with high viral loads (20). A phenotypically similar population was found to be significantly expanded in Malian individuals with persistent P. falciparum infections (21). Because the functionality of this population was not confirmed in the malaria cases, the population was called atypical MBC.…”

IFN-γ–Producing CD4+ T Cells Promote Generation of Protective Germinal Center–Derived IgM+ B Cell Memory against Salmonella Typhi

“…The results from the present S. Typhi porin immunization study suggest a remarkably simple regulation of B cell memory diversity in response to soluble porin proteins, namely, that repeated Ag application with provision of Ag for an ongoing GC reaction is a dominant factor in this process. Indeed, repeated application of soluble subunit vaccines would ideally mimic persisting low-level infections that are known to efficiently broaden B cell memory responses in humans (54). Importantly, an increase in B cell memory diversity further supports resistance of the host against infection through the generation of Abs against potential escape mutants (55).…”