Division of Biological and Biomedical Sciences, Washington University, St Louis, MO, USA.
Department of Immunobiology, University of Arizona College of Medicine, Tucson, AZ, USA.
Immunology. 2019 Feb;156(2):120-129. doi: 10.1111/imm.13019. Epub 2018 Nov 29.
The production of pathogen-specific B cells and antibodies underlies protective immunity elicited by most vaccines and many infections. Humoral immunity follows a regulated process by which high-affinity antibody-secreting plasma cells and memory B cells are generated. Yet for certain pathogens, protective immunity is inefficiently generated and/or maintained. For example, Dengue virus infections lead to lasting immunity against re-infection by the same serotype. However, if infected with a different Dengue serotype, the individual is predisposed to more severe disease than if he/she was completely naive. As another example, both natural infections with or vaccination against malaria do not necessarily lead to lasting immunity, as the same individual can be re-infected many times over the course of a lifetime. In this review, we discuss how these real-world problems can both instruct and be informed by recent basic studies using model organisms and antigens. An emphasis is placed on protective epitopes and functional distinctions between memory B-cell subsets in both mice and humans. Using flavivirus and Plasmodium infections as examples, we also speculate on the differences between ineffective B-cell responses that actually occur in the real world, and perfect-world responses that would generate lasting immunity.
病原体特异性 B 细胞和抗体的产生是大多数疫苗和许多感染引发保护性免疫的基础。体液免疫遵循一个受调控的过程，在此过程中会产生高亲和力的抗体分泌浆细胞和记忆 B 细胞。然而，对于某些病原体，保护性免疫的产生和/或维持效率低下。例如，登革热病毒感染会使人对同一血清型的再次感染产生持久免疫力。然而，如果感染了不同的登革热血清型，个体就容易患上比完全无免疫力时更严重的疾病。再如，疟疾的自然感染或疫苗接种不一定会产生持久的免疫力，因为同一个人在一生中可能会多次被感染。在这篇综述中，我们讨论了这些现实世界中的问题如何通过使用模式生物和抗原的最新基础研究来进行指导和提供信息。重点放在了保护性表位上，以及在小鼠和人类中记忆 B 细胞亚群之间的功能区别。我们以黄病毒和疟原虫感染为例，推测了实际发生在现实世界中的无效 B 细胞反应与产生持久免疫力的完美世界反应之间的区别。
