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 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.

Automated summary

This report introduces a new class of innate immune cells, called VIREMs, which are myeloid cells unrelated to lymphocytes. The researchers found that B-VIREMs, a subtype of VIREMs, have the ability to genetically recombine and express antibody genes, similar to B lymphocytes. They also discovered that B-VIREMs circulate in the blood of healthy individuals and undergo clonal expansion in response to disease stimuli. Live-cell imaging models suggest that B-VIREMs load their own Fc receptors with endogenous antibodies during vesicle transport. The findings suggest that these innate immune cells have important antigen-specific tissue maintenance functions.