Department of Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Department of Pediatrics, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
Cell Rep. 2020 Jan 14;30(2):351-366.e7. doi: 10.1016/j.celrep.2019.12.027.
Human rhinoviruses cause the common cold and exacerbate chronic respiratory diseases. Although infection elicits neutralizing antibodies, these do not persist or cross-protect across multiple rhinovirus strains. To analyze rhinovirus-specific B cell responses in humans, we developed techniques using intact RV-A16 and RV-A39 for high-throughput high-dimensional single-cell analysis, with parallel assessment of antibody isotypes in an experimental infection model. Our approach identified T-bet+ B cells binding both viruses that account for ∼5% of CXCR5- memory B cells. These B cells infiltrate nasal tissue and expand in the blood after infection. Their rapid secretion of heterotypic immunoglobulin G (IgG) in vitro, but not IgA, matches the nasal antibody profile post-infection. By contrast, CXCR5+ memory B cells binding a single virus are clonally distinct, absent in nasal tissue, and secrete homotypic IgG and IgA, mirroring the systemic response. Temporal and spatial functions of dichotomous memory B cells might explain the ability to resolve infection while rendering the host susceptible to re-infection.
人类鼻病毒会引起普通感冒，并使慢性呼吸道疾病恶化。尽管感染会引发中和抗体，但这些抗体不会持续存在，也不会在多种鼻病毒株之间交叉保护。为了分析人类鼻病毒特异性 B 细胞反应，我们使用完整的 RV-A16 和 RV-A39 开发了技术，用于高通量高维单细胞分析，并在实验感染模型中平行评估抗体同种型。我们的方法鉴定了 T-bet+B 细胞结合了两种病毒，占 CXCR5-记忆 B 细胞的约 5%。这些 B 细胞在感染后会浸润鼻组织并在血液中扩增。它们在体外快速分泌异源 IgG（IgG），而不是 IgA，与感染后鼻内的抗体谱相匹配。相比之下，结合单一病毒的 CXCR5+记忆 B 细胞是克隆性不同的，不存在于鼻组织中，并且分泌同型 IgG 和 IgA，反映了系统反应。二态记忆 B 细胞的时空功能可能解释了清除感染的能力，同时使宿主易受再感染的原因。
