Institute for Clinical Chemistry, University Medicine Mannheim, Mannheim, Germany.
Mannheim Institute of Innate Immunoscience, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany.
Sci Adv. 2023 Sep;9(35):eadg1812. doi: 10.1126/sciadv.adg1812. Epub 2023 Sep 1.
This report demonstrates a novel class of innate immune cells designated "variable immunoreceptor-expressing myeloids" (VIREMs). Using single-cell transcriptomics and genome-wide epigenetic profiling, we establish that VIREMs are myeloid cells unrelated to lymphocytes. We visualize the phenotype of B-VIREMs that are capable of genetically recombining and expressing antibody genes, the exclusive hallmark function of B lymphocytes. These cells, designated B-VIREMs, display monoclonal antibody cell surface signatures and regularly circulate in the blood of healthy individuals. Single-cell data reveal clonal expansion of circulating B-VIREMs as a dynamic response to disease stimuli. Live-cell imaging models suggest that B-VIREMs load their own Fc receptors with endogenous antibodies during vesicle transport to the cell surface. A first cloned B-VIREM-derived antibody (Vab1) specifically binds stomatin, a ubiquitous scaffold protein that is strictly expressed intracellularly, allowing Vab1-bearing macrophages to phagocytose cell debris without requiring prior opsonization. Our results suggest important antigen-specific tissue maintenance functionalities in these innate immune cells.
本报告展示了一类新型的固有免疫细胞，命名为“可变免疫受体表达髓系细胞”（Variable Immunoreceptor-Expressing Myeloids，VIREMs）。通过单细胞转录组学和全基因组表观遗传谱分析，我们确定 VIREMs 是与淋巴细胞无关的髓系细胞。我们观察到了具有基因重组和表达抗体基因能力的 B-VIREMs 的表型，这是 B 淋巴细胞独有的标志性功能。这些细胞被命名为 B-VIREMs，它们具有单克隆抗体的细胞表面特征，并且在健康个体的血液中经常循环。单细胞数据揭示了循环 B-VIREMs 的克隆扩增是对疾病刺激的动态反应。活细胞成像模型表明，B-VIREMs 在囊泡运输到细胞表面的过程中，将自身的 Fc 受体与内源性抗体结合。第一个克隆的 B-VIREM 衍生抗体（Vab1）特异性结合位于细胞内严格表达的泛素结合蛋白 stonatin，使携带 Vab1 的巨噬细胞能够吞噬细胞碎片，而无需预先调理。我们的结果表明，这些固有免疫细胞具有重要的抗原特异性组织维持功能。
