Opsonization-independent antigen-specific recognition by myeloid phagocytes expressing monoclonal antibodies.
Michael NeumaierSophie GieslerVolker AstMathis RoemerTimo-Daniel VossEileen ReinzVictor CostinaMartin SchmelzElina NürnbergStefanie NittkaAino-Maija LeppäRuediger RudolfFlavia Carla MeottiTina FuchsPublished in: Science advances (2023)
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.
Keyphrases
- single cell
- cell surface
- genome wide
- rna seq
- induced apoptosis
- immune response
- monoclonal antibody
- dna methylation
- high throughput
- cell cycle arrest
- acute myeloid leukemia
- bone marrow
- gene expression
- high resolution
- cell death
- oxidative stress
- signaling pathway
- stem cells
- transcription factor
- electronic health record
- cell therapy
- deep learning
- genome wide identification
- data analysis