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

Poulsen, Sofie Espersen ; Magda, Michal LU orcid ; Blom, Anna M. LU orcid and Nissen, Mogens Holst (2026) In Immunology Letters 282.
Abstract

Polymorphonuclear leukocytes (PMNs), predominantly neutrophil granulocytes, are key components of the innate immune system that eliminate invading pathogens through phagocytosis and clear apoptotic cells through efferocytosis. Beta-2-microglobulin (β2m) is best known as the light chain of major histocompatibility complex class I (MHC I), where it is required for antigen presentation to CD8⁺ T cells. However, emerging evidence suggests that extracellular β2m may also regulate innate immune responses. Here, we show that extracellular β2m enhances neutrophil phagocytosis and efferocytosis. Addition of soluble β2m (50 µg/ml) increased phagocytosis of latex beads by PMNs from 23% to 31%, whereas the proteolytically cleaved variant... (More)

Polymorphonuclear leukocytes (PMNs), predominantly neutrophil granulocytes, are key components of the innate immune system that eliminate invading pathogens through phagocytosis and clear apoptotic cells through efferocytosis. Beta-2-microglobulin (β2m) is best known as the light chain of major histocompatibility complex class I (MHC I), where it is required for antigen presentation to CD8⁺ T cells. However, emerging evidence suggests that extracellular β2m may also regulate innate immune responses. Here, we show that extracellular β2m enhances neutrophil phagocytosis and efferocytosis. Addition of soluble β2m (50 µg/ml) increased phagocytosis of latex beads by PMNs from 23% to 31%, whereas the proteolytically cleaved variant desLys58-β2m (dK58β2m) had no effect. In contrast, both β2m and dK58β2m enhanced phagocytosis of the Gram-positive bacterium Streptococcus pyogenes and the Gram-negative bacterium Acinetobacter baumannii by >3.6-fold. Furthermore, both β2m variants promoted efferocytosis of apoptotic Jurkat cells in a dose-dependent manner, resulting in up to a two-fold increase that was comparable to the effect of GM-CSF. Cytochalasin D abolished β2m-mediated uptake of apoptotic cells. Pre-incubation of latex beads with β2m followed by washing did not enhance phagocytosis, and pre-incubation of PMNs with β2m followed by washing did not enhance subsequent efferocytosis of apoptotic cells. These findings indicate that β2m does not act by coating phagocytic targets or by inducing sustained neutrophil priming. Collectively, these findings identify extracellular β2m as a regulator of neutrophil-mediated phagocytosis and efferocytosis and demonstrate that proteolytic processing differentially influences these activities.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Apoptotic cells, Bacteria, Beta-2-microglobulin, Innate immune system, Neutrophil, Phagocytosis
in
Immunology Letters
volume
282
article number
107221
publisher
Elsevier
external identifiers
  • pmid:42468854
  • scopus:105045886384
ISSN
0165-2478
DOI
10.1016/j.imlet.2026.107221
language
English
LU publication?
yes
id
a366a311-6e07-48fe-832d-3323f91d1a85
date added to LUP
2026-09-03 15:03:11
date last changed
2026-09-04 02:19:57
@article{a366a311-6e07-48fe-832d-3323f91d1a85,
  abstract     = {{<p>Polymorphonuclear leukocytes (PMNs), predominantly neutrophil granulocytes, are key components of the innate immune system that eliminate invading pathogens through phagocytosis and clear apoptotic cells through efferocytosis. Beta-2-microglobulin (β2m) is best known as the light chain of major histocompatibility complex class I (MHC I), where it is required for antigen presentation to CD8⁺ T cells. However, emerging evidence suggests that extracellular β2m may also regulate innate immune responses. Here, we show that extracellular β2m enhances neutrophil phagocytosis and efferocytosis. Addition of soluble β2m (50 µg/ml) increased phagocytosis of latex beads by PMNs from 23% to 31%, whereas the proteolytically cleaved variant desLys58-β2m (dK58β2m) had no effect. In contrast, both β2m and dK58β2m enhanced phagocytosis of the Gram-positive bacterium Streptococcus pyogenes and the Gram-negative bacterium Acinetobacter baumannii by &gt;3.6-fold. Furthermore, both β2m variants promoted efferocytosis of apoptotic Jurkat cells in a dose-dependent manner, resulting in up to a two-fold increase that was comparable to the effect of GM-CSF. Cytochalasin D abolished β2m-mediated uptake of apoptotic cells. Pre-incubation of latex beads with β2m followed by washing did not enhance phagocytosis, and pre-incubation of PMNs with β2m followed by washing did not enhance subsequent efferocytosis of apoptotic cells. These findings indicate that β2m does not act by coating phagocytic targets or by inducing sustained neutrophil priming. Collectively, these findings identify extracellular β2m as a regulator of neutrophil-mediated phagocytosis and efferocytosis and demonstrate that proteolytic processing differentially influences these activities.</p>}},
  author       = {{Poulsen, Sofie Espersen and Magda, Michal and Blom, Anna M. and Nissen, Mogens Holst}},
  issn         = {{0165-2478}},
  keywords     = {{Apoptotic cells; Bacteria; Beta-2-microglobulin; Innate immune system; Neutrophil; Phagocytosis}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Immunology Letters}},
  title        = {{Beta-2-microglobulin augments neutrophil phagocytosis of bacteria and apoptotic cells}},
  url          = {{http://dx.doi.org/10.1016/j.imlet.2026.107221}},
  doi          = {{10.1016/j.imlet.2026.107221}},
  volume       = {{282}},
  year         = {{2026}},
}