Department of Biomedicine, Division of Experimental Virology, University of Basel, Haus Petersplatz, 4009 Basel, Switzerland.
Development of the Immune System, Institut Necker-Enfants Malades, Institut National de la Santé et de la Recherche Médicale, U1151-Centre National de la Recherche Scientifique, UMR 8253, Faculté de Médecine Paris Descartes, Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Cell Rep. 2020 Jan 28;30(4):1013-1026.e7. doi: 10.1016/j.celrep.2019.12.023.
Persistent viral infections subvert key elements of adaptive immunity. To compare germinal center (GC) B cell responses in chronic and acute lymphocytic choriomeningitis virus infection, we exploit activation-induced deaminase (AID) fate-reporter mice and perform adoptive B cell transfer experiments. Chronic infection yields GC B cell responses of higher cellularity than acute infections do, higher memory B cell and antibody secreting cell output for longer periods of time, a better representation of the late B cell repertoire in serum immunoglobulin, and higher titers of protective neutralizing antibodies. GC B cells of chronically infected mice are similarly hypermutated as those emerging from acute infection. They efficiently adapt to viral escape variants and even in hypermutation-impaired AID mutant mice, chronic infection selects for GC B cells with hypermutated B cell receptors (BCRs) and neutralizing antibody formation. These findings demonstrate that, unlike for CD8 T cells, chronic viral infection drives a functional, productive, and protective GC B cell response.
持续性病毒感染颠覆了适应性免疫的关键要素。为了比较慢性和急性淋巴细胞脉络丛脑膜炎病毒感染中的生发中心（GC）B 细胞反应，我们利用激活诱导脱氨酶（AID）命运报告小鼠并进行过继性 B 细胞转移实验。慢性感染产生的 GC B 细胞反应比急性感染具有更高的细胞性，更长时间产生更高数量的记忆 B 细胞和抗体分泌细胞，在血清免疫球蛋白中更好地代表晚期 B 细胞库，以及更高滴度的保护性中和抗体。慢性感染小鼠的 GC B 细胞与急性感染中出现的 GC B 细胞一样发生了过度突变。它们能够有效地适应病毒逃逸变异体，甚至在 AID 突变小鼠中，慢性感染也会选择具有过度突变 B 细胞受体（BCR）和中和抗体形成的 GC B 细胞。这些发现表明，与 CD8 T 细胞不同，慢性病毒感染会引发功能性、有生产力和保护性的 GC B 细胞反应。
