The Francis Crick Institute, London, UK.
York Biomedical Research Institute, Hull York Medical School, University of York, York, UK.
Immunol Rev. 2020 Jan;293(1):57-69. doi: 10.1111/imr.12822. Epub 2019 Nov 16.
B-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.
B 细胞和抗体对疟原虫（引起疟疾的寄生虫）的反应对于控制寄生虫血症和相关免疫病理学至关重要。抗体也为再次感染提供保护。实验性模型感染和人类疟疾都表明，B 细胞对疟原虫的反应会产生持久的记忆。然而，有报道称，生活在疟疾中的幼儿对几种疟疾抗原的抗体反应并不具有同样的持久性，这表明循环抗体的维持存在功能障碍。一些研究将其归因于非典型记忆 B 细胞（AMB）的扩增，AMB 表达多种抑制性受体和激活标志物，并且在体外对 B 细胞受体（BCR）的再刺激反应性低。AMB 在其他慢性感染（如结核病、乙型和丙型肝炎以及 HIV）以及自身免疫和老年中也会扩增，这突出了了解其在免疫中的作用的重要性。AMB 是否存在功能障碍仍存在争议，因为其他感染的研究也表明，AMB 可以产生同种型转换的抗体，并且在小鼠中可以有助于预防感染。有鉴于此，我们回顾了辩论双方的最新文献，并对目前关于 B 细胞对疟原虫感染反应的一些观点提出了挑战。
