Protective immunity against atherosclerosis carried by B cells of hypercholesterolemic mice

Atherosclerosis is characterized by vascular inflammation and associated with systemic and local immune responses to oxidized LDL (oxLDL) and other antigens. Since immunization with oxLDL reduces atherosclerosis, we hypothesized that the disease might be associated with development of protective immunity. Here we show that spleen-associated immune activity protects against atherosclerosis. Splenectomy dramatically aggravated atherosclerosis in hypercholesterolemic apoE knockout (apoEdegrees) mice. Transfer of spleen cells from atherosclerotic apoEdegrees mice significantly reduced disease development in young apoEdegrees mice. To identify the protective subset, donor spleen cells were divided into B and T cells by immunomagnetic separation before transfer. Protection was conferred by B cells, which reduced disease in splenectomized apoEdegrees mice to one-fourth of that in splenectomized apoEdegrees controls. Protection could also be demonstrated in intact, nonsplenectomized mice and was associated with an increase in antibody titers to oxLDL. Fewer CD4(+) T cells were found in lesions of protected mice, suggesting a role for T-B cell cooperation. These results demonstrate that B cell-associated protective immunity develops during atherosclerosis and reduces disease progression.