Kinetics of B Cell Responses to Plasmodium falciparum Erythrocyte Membrane Protein 1 in Ghanaian Women Naturally Exposed to Malaria Parasites
Kinetics of B Cell Responses to Plasmodium falciparum Erythrocyte Membrane Protein 1 in Ghanaian Women Naturally Exposed to Malaria Parasites
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DOI：
10.4049/jimmunol.1400325
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发表时间：
2014-06-01
影响因子：
4.4
通讯作者：
Hviid, Lars
中科院分区：
文献类型：
--
作者：
Ampomah, Paulina;Stevenson, Liz;Hviid, Lars
对恶性疟疾自然获得的保护性免疫需要数年时间才能形成。它主要依赖于抗体，特别是针对感染的红细胞表面恶性疟原虫红细胞膜蛋白1(PfEMP1)的特异性免疫球蛋白。临床保护的获得需要数年时间才能形成，目前只有部分了解，但它可能涉及一系列免疫逃避寄生虫特征，尤其是PfEMP1多态和克隆变异。寄生虫诱导的免疫记忆颠覆和“非典型”记忆B细胞的扩张也可能起到作用。首先，据我们所知，在这类纵向研究中，我们测量了加纳妇女从早期怀孕到分娩后一年的B细胞亚群组成，以及PfEMP1特异性抗体水平和记忆性B细胞频率。在怀孕期间和怀孕后对细胞表型和抗原特异性B细胞功能进行了三次评估。妊娠受限的VAR2CSA型PfEMP1的特异性免疫球蛋白水平在妊娠期间显著增加，分娩后显著下降，而两种非妊娠限制性PfEMP1蛋白的特异性免疫球蛋白水平则没有变化。VAR2CSA特异性记忆B细胞频率的变化表现为典型的原始性记忆诱导和多孕期记忆扩张，然后是产后收缩。另外两种PfEMP1蛋白的记忆B细胞的频率没有系统性的变化。B细胞亚群分析证实了早先关于恶性疟原虫流行区居民中非典型记忆B细胞频率高的报道，并表明怀孕的另一种影响。我们的研究提供了关于对恶性疟原虫免疫的新知识，并支持了基于PfEMP1的疫苗的开发工作。
Naturally acquired protective immunity to Plasmodium falciparum malaria takes years to develop. It relies mainly on Abs, particularly IgG specific for Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) proteins on the infected erythrocyte surface. It is only partially understood why acquisition of clinical protection takes years to develop, but it probably involves a range of immune-evasive parasite features, not least of which are PfEMP1 polymorphism and clonal variation. Parasite-induced subversion of immunological memory and expansion of "atypical" memory B cells may also contribute. In this first, to our knowledge, longitudinal study of its kind, we measured B cell subset composition, as well as PfEMP1-specific Ab levels and memory B cell frequencies, in Ghanaian women followed from early pregnancy up to 1 y after delivery. Cell phenotypes and Ag-specific B cell function were assessed three times during and after pregnancy. Levels of IgG specific for pregnancy-restricted, VAR2CSA-type PfEMP1 increased markedly during pregnancy and declined after delivery, whereas IgG levels specific for two PfEMP1 proteins not restricted to pregnancy did not. Changes in VAR2CSA-specific memory B cell frequencies showed typical primary memory induction among primigravidae and recall expansion among multigravidae, followed by contraction postpartum in all. No systematic changes in the frequencies of memory B cells specific for the two other PfEMP1 proteins were identified. The B cell subset analysis confirmed earlier reports of high atypical memory B cell frequencies among residents of P. falciparum-endemic areas, and indicated an additional effect of pregnancy. Our study provides new knowledge regarding immunity to P. falciparum malaria and underpins efforts to develop PfEMP1-based vaccines against this disease.