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 ...