Department of Microbiology and Immunology, The University of Iowa, Iowa City, IA.
Department of Medicine, Section of Rheumatology, The University of Chicago, Chicago, IL.
J Exp Med. 2021 Jun 7;218(6). doi: 10.1084/jem.20202359.
Antimalarial antibody responses are essential for mediating the clearance of Plasmodium parasite-infected RBCs from infected hosts. However, the rapid appearance of large numbers of plasmablasts in Plasmodium-infected hosts can suppress the development and function of durable humoral immunity. Here, we identify that the formation of plasmablast populations in Plasmodium-infected mice is mechanistically linked to both hemolysis-induced exposure of phosphatidylserine on damaged RBCs and inflammatory cues. We also show that virus and Trypanosoma infections known to trigger hemolytic anemia and high-grade inflammation also induce exuberant plasmablast responses. The induction of hemolysis or administration of RBC membrane ghosts increases plasmablast differentiation. The phosphatidylserine receptor Axl is critical for optimal plasmablast formation, and blocking phosphatidylserine limits plasmablast expansions and reduces Plasmodium parasite burden in vivo. Our findings support that strategies aimed at modulating polyclonal B cell activation and phosphatidylserine exposure may improve immune responses against Plasmodium parasites and potentially other infectious diseases that are associated with anemia.
抗疟抗体反应对于介导从感染宿主中清除疟原虫寄生虫感染的 RBC 至关重要。然而，大量浆母细胞在疟原虫感染宿主中的快速出现会抑制持久体液免疫的发展和功能。在这里，我们确定在疟原虫感染的小鼠中浆母细胞群体的形成与溶血诱导的损伤 RBC 上磷脂酰丝氨酸的暴露以及炎症信号有关。我们还表明，已知引发溶血性贫血和高度炎症的病毒和锥虫感染也会引发过度的浆母细胞反应。溶血的诱导或 RBC 膜幽灵的给药会增加浆母细胞的分化。磷脂酰丝氨酸受体 Axl 对于最佳浆母细胞形成至关重要，而阻断磷脂酰丝氨酸会限制浆母细胞的扩增并减少体内疟原虫寄生虫负担。我们的研究结果支持这样一种观点，即旨在调节多克隆 B 细胞激活和磷脂酰丝氨酸暴露的策略可能会改善针对疟原虫寄生虫和其他可能与贫血相关的传染病的免疫反应。
