Rationale: Deficiency of secreted IgM (sIgM-/-) accelerates atherosclerosis in Ldlr-/-mice. Several
atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing
inflammation induced by oxidized LDL and promoting apoptotic cell clearance. However, the mechanisms
by which the lack of sIgM promotes lesion formation remain unknown.
Objective: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice.
Methods and Results: We here show that both sIgM-/- and Ldlr-/-sIgM-/- mice develop increased plasma IgE
titers due to impaired generation of B cells expressing the low affinity IgE receptor CD23, which mediates
the clearance of IgE antibodies. We further report that Ldlr-/-sIgM-/- mice exhibit increased numbers of
activated mast cells and neutrophils in the perivascular area...
Show more Rationale: Deficiency of secreted IgM (sIgM-/-) accelerates atherosclerosis in Ldlr-/-mice. Several
atheroprotective effects of increased levels of IgM antibodies have been suggested, including preventing
inflammation induced by oxidized LDL and promoting apoptotic cell clearance. However, the mechanisms
by which the lack of sIgM promotes lesion formation remain unknown.
Objective: To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice.
Methods and Results: We here show that both sIgM-/- and Ldlr-/-sIgM-/- mice develop increased plasma IgE
titers due to impaired generation of B cells expressing the low affinity IgE receptor CD23, which mediates
the clearance of IgE antibodies. We further report that Ldlr-/-sIgM-/- mice exhibit increased numbers of
activated mast cells and neutrophils in the perivascular area of atherosclerotic plaques. Treatment with an
anti-IgE neutralizing antibody fully reversed vascular inflammation and accelerated atherosclerotic lesion
formation in cholesterol-fed Ldlr-/-sIgM-/- mice.
Conclusions: Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency
aggravates atherosclerosis.
Keywords:
Atherosclerosis, secreted IgM, IgE, B cells, arteriosclerosis, immune system, antibody, inflammation.
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