Raphael A Reyes, Louise Turner, Isaac Ssewanyana, Prasanna Jagannathan, Margaret E Feeney, Thomas Lavstsen, Bryan Greenhouse, Sebastiaan Bol, Evelien M Bunnik
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引用次数: 0
Abstract
Plasmodium falciparum infections elicit strong humoral immune responses to two main groups of antigens expressed by blood-stage parasites: merozoite antigens that are involved in the erythrocyte invasion process and variant surface antigens that mediate endothelial sequestration of infected erythrocytes. Long-lived B cells against both antigen classes can be detected in the circulation for years after exposure, but have not been directly compared. Here, we studied the phenotype of long-lived memory and atypical B cells to merozoite antigens (MSP1 and AMA1) and variant surface antigens (the CIDRα1 domain of PfEMP1) in ten Ugandan adults before and after local reduction of P. falciparum transmission. After a median of 1.7 years without P. falciparum infections, the percentage of antigen-specific activated B cells declined, but long-lived antigen-specific B cells were still detectable in all individuals. The majority of MSP1/AMA1-specific B cells were CD95+CD11c+ memory B cells, which are primed for rapid differentiation into antibody-secreting cells, and FcRL5-T-bet- atypical B cells. On the other hand, most CIDRα1-specific B cells were CD95-CD11c- memory B cells. CIDRα1-specific B cells were also enriched among a subset of atypical B cells that seem poised for antigen presentation. These results point to differences in how these antigens are recognized or processed by the immune system and how P. falciparum-specific B cells will respond upon re-infection.
恶性疟原虫感染会引起对血型寄生虫所表达的两大类抗原的强烈体液免疫反应:参与红细胞侵袭过程的子虫抗原和介导内皮细胞封闭受感染红细胞的变异表面抗原。两种抗原的长效 B 细胞在暴露后数年仍可在血液循环中检测到,但尚未进行直接比较。在此,我们研究了十名乌干达成年人在当地恶性疟原虫传播减少之前和之后,针对虫体抗原(MSP1 和 AMA1)和变体表面抗原(PfEMP1 的 CIDRα1 结构域)的长效记忆和非典型 B 细胞的表型。在没有感染恶性疟原虫的中位数 1.7 年后,抗原特异性活化 B 细胞的百分比下降,但在所有个体中仍能检测到长效抗原特异性 B 细胞。大多数 MSP1/AMA1 特异性 B 细胞是 CD95+CD11c+ 记忆 B 细胞(可快速分化为分泌抗体的细胞)和 FcRL5-T-bet- 非典型 B 细胞。另一方面,大多数 CIDRα1 特异性 B 细胞是 CD95-CD11c- 记忆 B 细胞。CIDRα1特异性B细胞还富集在非典型B细胞亚群中,这些亚群似乎已准备好进行抗原呈递。这些结果表明,免疫系统识别或处理这些抗原的方式存在差异,恶性疟原虫特异性 B 细胞在再次感染时会做出何种反应。
期刊介绍:
Bacteria, fungi, parasites, prions and viruses cause a plethora of diseases that have important medical, agricultural, and economic consequences. Moreover, the study of microbes continues to provide novel insights into such fundamental processes as the molecular basis of cellular and organismal function.