Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency.

Rationale: Deficiency of secreted IgM (sIgM) accelerates atherosclerosis in Ldlrmice. 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 LdlrsIgM 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 LdlrsIgM 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 LdlrsIgM mice.

Conclusions: Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency aggravates atherosclerosis.