Lymph node (LN) germinal centers (GCs) are critical sites for B cell activation and differentiation. GCs develop after specialized CD169⁺ macrophages residing in LN sinuses filter antigens (Ags) from the lymph and relay these Ags into proximal B cell follicles. Many viruses, however, first reach LNs through the blood during viremia (virus in the blood), rather than through lymph drainage from infected tissue. How LNs capture viral Ag from the blood to allow GC development is not known. Here, we followed Zika virus (ZIKV) dissemination in mice and subsequent GC formation in both infected tissue–draining and non-draining LNs. From the footpad, ZIKV initially disseminated through two LN chains, infecting LN macrophages and leading to GC formation. Despite rapid ZIKV viremia, non-draining LNs were not infected for several days. Non-draining LN infection correlated with virus-induced vascular leakage and neutralization of permeability reduced LN macrophage attrition. Depletion of non-draining LN macrophages significantly decreased GC B cells in these nodes. Thus, although LNs inefficiently captured viral Ag directly from the blood, GC formation in non-draining LNs proceeded similarly to draining LNs through LN sinus CD169⁺ macrophages. Together, our findings reveal a conserved pathway allowing LN macrophages to activate antiviral B cells in LNs distal from infected tissue after blood-borne viral infection.

中文翻译：

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血源性病毒感染期间，被膜下窦巨噬细胞最大限度地促进非引流淋巴结生发中心的发育

淋巴结 (LN) 生发中心 (GC) 是 B 细胞激活和分化的关键部位。位于淋巴结窦中的专门 CD169 ⁺巨噬细胞从淋巴中过滤抗原 (Ag) 并将这些 Ag 传递到近端 B 细胞滤泡中，从而形成 GC。然而，许多病毒在病毒血症（血液中的病毒）期间首先通过血液到达淋巴结，而不是通过受感染组织的淋巴引流。LN 如何从血液中捕获病毒 Ag 以促进 GC 发育尚不清楚。在这里，我们跟踪了寨卡病毒 (ZIKV) 在小鼠中的传播以及随后在受感染组织引流和非引流淋巴结中的 GC 形成。ZIKV 最初从足垫通过两条 LN 链传播，感染 LN 巨噬细胞并导致 GC 形成。尽管 ZIKV 病毒血症迅速出现，但非引流淋巴结在几天内都没有被感染。非引流性淋巴结感染与病毒诱导的血管渗漏和渗透性中和减少了淋巴结巨噬细胞的消耗相关。非引流 LN 巨噬细胞的消耗显着减少了这些节点中的 GC B 细胞。因此，尽管 LN 直接从血液中捕获病毒 Ag 的效率较低，但非引流 LN 中 GC 的形成过程与通过 LN 窦 CD169 ⁺巨噬细胞引流 LN 的过程类似。总之，我们的研究结果揭示了一条保守的途径，允许 LN 巨噬细胞在血源性病毒感染后激活远离感染组织的 LN 中的抗病毒 B 细胞。