DOI: 10.1126/sciadv.adg1812 ISSN:

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

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
  • Multidisciplinary

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.

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