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Circulating IgM Requires Plasma Membrane Disruption to Bind Apoptotic and
Non-Apoptotic Nucleated Cells and Erythrocytes
#MMPMID26121639
Hesketh EE
; Dransfield I
; Kluth DC
; Hughes J
PLoS One
2015[]; 10
(6
): e0131849
PMID26121639
show ga
Autoimmunity is associated with defective phagocytic clearance of apoptotic
cells. IgM deficient mice exhibit an autoimmune phenotype consistent with a role
for circulating IgM antibodies in apoptotic cell clearance. We have extensively
characterised IgM binding to non-apoptotic and apoptotic mouse thymocytes and
human Jurkat cells using flow cytometry, confocal imaging and electron
microscopy. We demonstrate strong specific IgM binding to a subset of Annexin-V
(AnnV)+PI (Propidium Iodide)+ apoptotic cells with disrupted cell membranes.
Electron microscopy studies indicated that IgM+AnnV+PI+ apoptotic cells exhibited
morphologically advanced apoptosis with marked plasma membrane disruption
compared to IgM-AnnV+PI+ apoptotic cells, suggesting that access to intracellular
epitopes is required for IgM to bind. Strong and comparable binding of IgM to
permeabilised non-apoptotic and apoptotic cells suggests that IgM bound epitopes
are 'apoptosis independent' such that IgM may bind any cell with profound
disruption of cell plasma membrane integrity. In addition, permeabilised
erythrocytes exhibited significant IgM binding thus supporting the importance of
cell membrane epitopes. These data suggest that IgM may recognize and tag damaged
nucleated cells or erythrocytes that exhibit significant cell membrane
disruption. The role of IgM in vivo in conditions characterized by severe cell
damage such as ischemic injury, sepsis and thrombotic microangiopathies merits
further exploration.
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