B-Cell Aortic Homing and Atheroprotection Depend on Id3

Abstract

Rationale:B cells are abundant in the adventitia of normal and diseased vessels. Yet, the molecular and cellular mechanisms mediating homing of B cells to the vessel wall and B-cell effects on atherosclerosis are poorly understood. Inhibitor of differentiation-3 (Id3) is important for atheroprotection in mice and polymorphism in the human ID3 gene has been implicated as a potential risk marker of atherosclerosis in humans. Yet, the role of Id3 in B-cell regulation of atherosclerosis is unknown. Objective:To determine if Id3 regulates B-cell homing to the aorta and atheroprotection and identify molecular and cellular mechanisms mediating this effect. Methods and Results:Loss of Id3 in Apoe−/− mice resulted in early and increased atherosclerosis. Flow cytometry revealed a defect in Id3−/− Apoe−/− mice in the number of B cells in the aorta but not the spleen, lymph nodes, and circulation. Similarly, B cells transferred from Id3−/− Apoe−/− mice into B-cell–deficient mice reconstituted spleen, lymph node, and ...