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Increased Plasma IgE Accelerate Atherosclerosis in Secreted IgM Deficiency

D. Tsiantoulas,I. Bot,M. Ozsvár-Kozma,L. Göderle,T. Perkmann,K. Hartvigsen,D. Conrad,J. Kuiper,Z. Mallat,C. Binder

Published 2017 in Circulation Research

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.

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