Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency

Abstract

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.