B-1b Cells Secrete Atheroprotective IgM and Attenuate Atherosclerosis

Rationale:B cells contribute to atherosclerosis through subset-specific mechanisms. Whereas some controversy exists about the role of B-2 cells, B-1a cells are atheroprotective because of secretion of atheroprotective IgM antibodies independent of antigen. B-1b cells, a unique subset of B-1 cells that respond specifically to T-cell–independent antigens, have not been studied within the context of atherosclerosis. Objective:To determine whether B-1b cells produce atheroprotective IgM antibodies and function to protect against diet-induced atherosclerosis. Methods and Results:We demonstrate that B-1b cells are sufficient to produce IgM antibodies against oxidation-specific epitopes on low-density lipoprotein both in vitro and in vivo. In addition, we demonstrate that B-1b cells provide atheroprotection after adoptive transfer into B- and T-cell deficient (Rag1−/−Apoe−/−) hosts. We implicate inhibitor of differentiation 3 (Id3) in the regulation of B-1b cells as B-cell–specific Id3 knockout mice (Id3BKOApoe−...