Studies have established a role for T cells in resolving persistent viral infections, yet emerging evidence indicates that both T and B cells are required to control some viruses. During persistent infection, a marked lag or failure to generate neutralizing antibodies is commonly observed and likely contributes to an inability to control certain pathogens. Using lymphocytic choriomeningitis virus (LCMV) as a model, we have examined how a persistent viral infection can suppress neutralizing humoral immunity. By tracking the fate of virus-specific B cells in vivo, we report that LCMV-specific B cells were rapidly deleted within a few days of persistent infection, and this deletion was completely reversed by blockade of type I interferon (IFN-I) signaling. Early interference with IFN-I signaling promoted survival and differentiation of LCMV-specific B cells, which accelerated the generation of neutralizing antibodies. This marked improvement in antiviral humoral immunity did not rely on the cessation of IFN-I signaling in B cells but on alterations in the virus-specific CD8+ T cell response. Using two-photon microscopy and in vivo calcium imaging, we observed that cytotoxic T lymphocytes (CTLs) productively engaged and killed LCMV-specific B cells in a perforin-dependent manner within the first few days of infection. Blockade of IFN-I signaling protected LCMV-specific B cells by promoting CTL dysfunction. Therapeutic manipulation of this pathway may facilitate efforts to promote humoral immunity during persistent viral infection in humans. Our findings illustrate how events that occur early after infection can disturb the resultant adaptive response and contribute to viral persistence.

中文翻译：

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I 型干扰素通过调节 CD8+ T 细胞分化来抑制病毒特异性 B 细胞反应。

研究已经确定了 T 细胞在解决持续性病毒感染方面的作用，但新出现的证据表明，控制某些病毒需要 T 细胞和 B 细胞。在持续感染期间，通常会观察到明显滞后或无法产生中和抗体，这可能导致无法控制某些病原体。使用淋巴细胞脉络丛脑膜炎病毒 (LCMV) 作为模型，我们研究了持续性病毒感染如何抑制中和体液免疫。通过在体内追踪病毒特异性 B 细胞的命运，我们报告说 LCMV 特异性 B 细胞在持续感染的几天内被迅速删除，并且这种删除被 I 型干扰素 (IFN-I) 信号传导的阻断完全逆转. 对 IFN-I 信号的早期干扰促进了 LCMV 特异性 B 细胞的存活和分化，从而加速了中和抗体的产生。抗病毒体液免疫的这种显着改善并不依赖于 B 细胞中 IFN-I 信号的停止，而是依赖于病毒特异性 CD8+ T 细胞反应的改变。使用双光子显微镜和体内钙成像，我们观察到细胞毒性 T 淋巴细胞 (CTL) 在感染的前几天内以穿孔素依赖性方式有效地参与和杀死 LCMV 特异性 B 细胞。阻断 IFN-I 信号通过促进 CTL 功能障碍来保护 LCMV 特异性 B 细胞。对该途径的治疗操作可能有助于在人类持续病毒感染期间促进体液免疫。