Detection of B cells and proinflammatory cytokines in atherosclerotic plaques of hypercholesterolaemic apolipoprotein E knockout mice

Atherosclerosis, the main lethal disease in the Western world, is associate d with a cellular immune response in the arterial lesions and a humoral imm une response directed towards oxidized lipoproteins, certain microbes and o ther antigens. The local immune response is dominated by macrophages and T cells, while to date, the role of B cells in lesions has been unclear. We a nalysed B-cell involvement in lesions using the apolipoprotein E knockout m ouse, an experimental model that develops accelerated atherosclerosis when fed a lipid-rich diet. Both early fatty-streak-type lesions and full-blown atherosclerotic plaques of these mice contained CD22(+) B cells. They accum ulated predominantly in the base of lesions, where high expression levels o f vascular cell adhesion molecule-1 (VCAM-1) were observed in other cells. Cells expressing interleukin-6 and tumour necrosis factor-or were also dete cted and IgM was abundant in this region. These data show that B cells part icipate in atherosclerosis in this experimental model; the data also sugges t that these cells may accumulate through VCAM-1 expression by surrounding cells and may produce antibodies and proinflammatory cytokines. These facto rs are likely to be important in the pathogenesis of atherosclerosis.