Bond Annalise, Fiaz Sareen, Rollins Kirstin R, Nario Jazz Elaiza Q, Rosen Samuel J, Granados Alyssa, Wilson Maxwell Z, Morrissey Meghan A
Molecular Cellular and Developmental Biology Department, University of California, Santa Barbara, Santa Barbara CA.
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bioRxiv. 2023 Nov 14:2023.11.14.567059. doi: 10.1101/2023.11.14.567059.
Macrophages measure the 'eat-me' signal IgG to identify targets for phagocytosis. We wondered if prior encounters with IgG influence macrophage appetite. IgG is recognized by the Fc Receptor. To temporally control Fc Receptor activation, we engineered an Fc Receptor that is activated by light-induced oligomerization of Cry2, triggering phagocytosis. Using this tool, we demonstrate that Fc Receptor activation primes macrophages to be more sensitive to IgG in future encounters. Macrophages that have previously experienced Fc Receptor activation eat more IgG-bound cancer cells. Increased phagocytosis occurs by two discrete mechanisms - a short- and long-term priming. Long term priming requires new protein synthesis and Erk activity. Short term priming does not require new protein synthesis and correlates with an increase in Fc Receptor mobility. Our work demonstrates that IgG primes macrophages for increased phagocytosis, suggesting that therapeutic antibodies may become more effective after initial priming doses.
巨噬细胞通过检测“吃掉我”信号免疫球蛋白G（IgG）来识别吞噬目标。我们想知道之前接触IgG是否会影响巨噬细胞的吞噬能力。IgG可被Fc受体识别。为了在时间上控制Fc受体的激活，我们构建了一种Fc受体，它可通过光诱导的隐花色素2（Cry2）寡聚化而被激活，从而触发吞噬作用。利用这一工具，我们证明Fc受体的激活使巨噬细胞在未来接触中对IgG更加敏感。之前经历过Fc受体激活的巨噬细胞会吞噬更多与IgG结合的癌细胞。吞噬作用的增强通过两种不同的机制实现——短期和长期致敏。长期致敏需要新的蛋白质合成和细胞外信号调节激酶（Erk）活性。短期致敏不需要新的蛋白质合成，且与Fc受体流动性的增加相关。我们的研究表明，IgG使巨噬细胞的吞噬作用增强，这表明治疗性抗体在初始致敏剂量后可能会变得更有效。
