Opsonization-independent antigen-specific recognition by myeloid phagocytes expressing monoclonal antibodies

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...

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Main Authors: Neumaier, Michael (Author) , Giesler, Sophie (Author) , Ast, Volker (Author) , Römer, Mathis (Author) , Voß, Timo-Daniel (Author) , Reinz, Eileen (Author) , Costina, Victor (Author) , Schmelz, Martin (Author) , Nürnberg, Elina (Author) , Nittka, Stefanie (Author) , Leppä, Aino-Maija (Author) , Rudolf, Rüdiger (Author) , Trumpp, Andreas (Author) , Fuchs, Tina (Author)
Format: Article (Journal)
Language:English
Published: Sep 2023
In: Science advances
Year: 2023, Volume: 9, Issue: 35, Pages: 1-12
ISSN:2375-2548
DOI:10.1126/sciadv.adg1812
Online Access:Resolving-System, kostenfrei: https://doi.org/10.1126/sciadv.adg1812
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Author Notes:Michael Neumaier, Sophie Giesler, Volker Ast, Mathis Roemer, Timo-Daniel Voß, Eileen Reinz, Victor Costina, Martin Schmelz, Elina Nürnberg, Stefanie Nittka, Aino-Maija Leppä, Ruediger Rudolf, Andreas Trumpp, Tina Fuchs
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Summary: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.
Item Description:Online veröffentlicht: 01. September 2023
Gesehen am 09.11.2023
Physical Description:Online Resource
ISSN:2375-2548
DOI:10.1126/sciadv.adg1812