中文摘要：

在流感病毒继发感染期间，浆细胞 （PCs） 在肺内发育，提供局部抗体来源。然而，调节这一过程的场所和机制定义不明确。在这里，我们表明，虽然循环记忆 B 细胞在再攻击期间进入肺部并在诱导性支气管相关淋巴组织 （iBALTs） 内被激活，但常驻记忆 B （BRM） 细胞反应更早，并且它们的激活发生在不同的生态位：直接靠近受感染的肺泡。这个过程需要 NK 细胞，但在很大程度上独立于 CD4 和 CD8 T 细胞。在没有同源抗原的情况下，含有 ssRNA 的病毒样颗粒诱导的先天刺激触发了 BRM 细胞分化，表明激活阈值较低。相比之下，iBALTs 中 PC 的扩增需要更长的时间来发展，并且严重依赖于 CD4 T 细胞。我们的工作表明，空间上不同的机制进化为支持肺部继发性 PC 反应，并揭示了 BRM 细胞作为肺泡守护者的特殊功能。

英文摘要：

During secondary infection with influenza virus, plasma cells (PCs) develop within the lung, providing a local source of antibodies. However, the site and mechanisms that regulate this process are poorly defined. Here, we show that while circulating memory B cells entered the lung during rechallenge and were activated within inducible bronchus-associated lymphoid tissues (iBALTs), resident memory B (BRM) cells responded earlier, and their activation occurred in a different niche: directly near infected alveoli. This process required NK cells but was largely independent of CD4 and CD8 T cells. Innate stimuli induced by virus-like particles containing ssRNA triggered BRM cell differentiation in the absence of cognate antigen, suggesting a low threshold of activation. In contrast, expansion of PCs in iBALTs took longer to develop and was critically dependent on CD4 T cells. Our work demonstrates that spatially distinct mechanisms evolved to support pulmonary secondary PC responses, and it reveals a specialized function for BRM cells as guardians of the alveoli.

论文信息：

论文题目： Regulation of pulmonary plasma cell responses during secondary infection with influenza virus

期刊名称：JEM- J Exp Med

时间期卷： J Exp Med (2024) 221 (7): e20232014.

在线时间：2024年4月25日

DOI： doi.org/10.1084/jem.20232014

Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于JEM：

Liposoma巨噬细胞清除剂Clodronate Liposomes的材料和方法：

JEM流感病毒继发感染模型肺泡巨噬细胞清除解决方案

Clodronate liposomes (SKU: C-005) and PBS liposomes(SKU: P-005) were commercially available and purchasedfrom Liposoma BV . The concentration of the clodronatein the suspension was 5 mg/ml. Liposome suspensions were injected directly without any further dilutions.  Alveolar macrophages were depleted using IN administration of clodronated liposomes (CLL). 45 μl dosage of Clodrosome (Liposoma BV) was administered IN twice 6 days prior to rechallenge and twice 3 days before rechallenge. The selective depletion of alveolar macrophages using this approach was based on previous works (Leemans et al., 2001) and was optimized in our own hands as described in our recent publication (MacLean et al., 2022). It should be noted that we cannot exclude the possibility that small amounts of CLL that may not been sufficient to kill interstitial phagocytes have reached the parenchyma, potentially compromising neutrophil functionality (Culemann et al., 2023).