Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency

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 low-density lipoprotein 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 because of 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.