B-cell memory in malaria: Myths and realities.

Damián Pérez-Mazliah,Racheal Aye,Francis M Ndungu,Jean Langhorne

doi:10.1111/imr.12822

Abstract

SummaryB‐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.

Highlights

Malaria is a killer disease caused by infection with species of the protozoan parasite, Plasmodium
The most deadly of these parasites is Plasmodium falciparum, for which the estimates of morbidity and mortality in Africa were 219 million and 435 000, respectively, in 2017.1 several control methods have been employed with substantial success, malaria continues to place a heavy burden on the health systems and economies of the countries affected
CD4+ T cells producing IL‐21, a characteristic cytokine of Tfh, and Tfh defined by expression of PD‐1 and CXCR5 are present in peripheral blood mononuclear cells from malaria‐exposed im‐ mune adults[118,119,120] and in some cases, correlate with P falciparum‐ specific IgG antibodies in children with acute P. falciparum malaria.[121]

Summary

INVITED REVIEW

Funding information MRC/DFID African Research Leadership Award; DELTAS Africa Initiative, Grant/ Award Number: DEL‐15‐003; Medical Research Council, Grant/Award Number: FC 10101; Hull York Medical School, UK; Cancer Research UK, Grant/Award Number: FC 10101; Wellcome Trust, Grant/Award Number: 107499/Z/15/Z, 107769/Z/10/Z, FC 10101 and WT104777/Z/14/Z. There are reports that antibody responses to several malaria an‐ tigens in young children living with malaria are not 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 in‐ hibitory receptors and activation markers, and are hyporesponsive to B‐cell receptor (BCR) restimulation in vitro. Whether AMB are dysfunctional remains controversial, as there are studies in other infections showing that AMB can produce isotype‐switched antibodies and in mouse can con‐ tribute 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 cur‐ rently held views regarding B‐cell responses to Plasmodium infections. KEYWORDS classical and atypical memory B cells, long‐lived plasma cells, malaria, Plasmodium

| INTRODUCTION

Findings

| CONCLUDING REMARKS