T-bet–expressing B cells promote atherosclerosis in apolipoprotein E–deficient mice

The humoral immune system influences the development of atherosclerosis, but the contributions of specific memory B cell subsets and IgG isotypes are poorly understood. We assessed the relationship between atherosclerosis and age-associated B cells (ABCs), a T-bet-expressing memory B cell subset that is enriched for IgG2c production and implicated in humoral autoimmunity. We found increased numbers of splenic CD11c+ ABCs in 6-mo-old, chow-fed Apoe-/- mice versus C57BL/6 control mice, which were exacerbated by high-fat diet. Deletion of T-bet in the B lineage in high-fat diet-fed Apoe-/- mice reduced aortic lesion area, and this correlated with decreased splenic CD11c+ B cells and reduced serum oxidized low-density lipoprotein-specific IgG2c. Our findings suggest that T-bet-expressing B cells are atherogenic agents in the Apoe-/- model and indicate that interventions to inhibit a T-bet-driven humoral response may improve atherosclerotic disease.