Young Lives Lost as B Cells Falter: What We Are Learning About Antibody Responses in Malaria

Abstract

Plasmodium falciparum malaria remains a major public health threat for which there is no licensed vaccine. Abs play a key role in malaria immunity, but Ab-mediated protection is only acquired after years of repeated infections, leaving children in endemic areas vulnerable to severe malaria and death. Many P. falciparum Ags are extraordinarily diverse and clonally variant, which likely contribute to the inefficient acquisition of protective Abs. However, mounting evidence suggests that there is more to the story and that infection-induced dysregulation of B cell function also plays a role. We herein review progress toward understanding the B cell biology of P. falciparum infection, focusing on what has been learned from population-based studies in malaria-endemic areas. We suggest ways in which advances in immunology and genomics-based technology can further improve our understanding of the B cell response in malaria and perhaps illuminate new pathways to the development of effective vaccines.