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bioRxiv · 10.1101/2025.10.30.685267

Beta-2-microglobulin stimulates neutrophil phagocytosis of bacteria and apoptotic cells

Poulsen, S. E.·Magda, M.·Blom, A.·Nissen, M. H.
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Abstract

Efficient clearance of dead cells and pathogens is essential for survival and requires both the innate and adaptive immune systems. Polymorphonuclear leukocytes (PMNs, predominantly consisting of neutrophil granulocytes) constitute an important first line of defense. These highly specialized cells can phagocytose pathogens and clear apoptotic cells through efferocytosis. Beta-2-microglobulin ({beta}2m) serves as the light chain of major histocompatibility complex class I (MHC I) molecules, associating non-covalently with the heavy transmembrane chain that binds and presents antigenic peptides to CD8+ T cells. This represents the canonical role of {beta}2m. {beta}2m is also found in the granules of PMNs and is released into the extracellular space during degranulation. However, a specific function for {beta}2m in the context of PMN function or degranulation has not yet been identified. We now present evidence that {beta}2m is of importance for both phagocytosis of pathogens and efferocytosis of dead cells by PMNs. The addition of exogenous {beta}2m (50 mg/l) to PMNs in the presence of latex beads increased the phagocytic activity from 23% to 31%. Furthermore, both {beta}2m and desLys58-{beta}2m (dK58{beta}2m) enhanced phagocytosis of Gram-negative and -positive bacteria by more than 3.6-fold, though no effect was observed with zymosan bioparticles. Maintaining tissue homeostasis requires the continuous generation of new cells and the efficient clearance of apoptotic cells through efferocytosis. Treatment with {beta}2m or dK58{beta}2m led to a dose-dependent increase in efferocytosis of apoptotic Jurkat cells, reaching up to a two-fold enhancement. This effect was comparable to that obtained by GM-CSF, used as a positive control. In all cases, cytochalasin D blocked {beta}2m-mediated uptake in PMNs. These data demonstrate that {beta}2m can be of importance in phagocytosis of bacterial pathogens as part of the innate immune response and tissue homeostasis by removing dead cells by efferocytosis.

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Poulsen, S. E., Magda, M., Blom, A., Nissen, M. H.. 2025-10-31. Beta-2-microglobulin stimulates neutrophil phagocytosis of bacteria and apoptotic cells. https://doi.org/10.1101/2025.10.30.685267

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