Studies on the role of B lymphocytes in
atherosclerosis development, have yielded contradictory results. Whereas B lymphocyte-deficiency aggravates
atherosclerosis in mice; depletion of mature B lymphocytes reduces
atherosclerosis. These observations led to the notion that distinct B lymphocyte subsets have different roles. B1a lymphocytes exert an atheroprotective effect, which has been attributed to secretion of
IgM, which can be deposited in atherosclerotic lesions thereby reducing necrotic core formation.
Tumor necrosis factor (TNF)-family member 'A Proliferation-Inducing
Ligand' (APRIL, also known as TNFSF13) was previously shown to increase serum
IgM levels in a murine model. In this study, we investigated the effect of APRIL overexpression on advanced lesion formation and composition,
IgM production and B cell phenotype. We crossed APRIL transgenic (APRIL-Tg) mice with
ApoE knockout (
ApoE-/-) mice. After a 12-week Western Type Diet,
ApoE-/-APRIL-Tg mice and
ApoE-/- littermates showed similar increases in
body weight and
lipid levels. Histologic evaluation showed no differences in lesion size, stage or necrotic area. However, smooth muscle cell (α-actin
stain) content was increased in
ApoE-/-APRIL-Tg mice, implying more stable lesions. In addition, increases in both plaque
IgM deposition and plasma
IgM levels were found in
ApoE-/-APRIL-Tg mice compared with
ApoE-/- mice. Flow cytometry revealed a concomitant increase in peritoneal B1a lymphocytes in
ApoE-/-APRIL-Tg mice. This study shows that
ApoE-/-APRIL-Tg mice have increased
oxLDL-specific serum
IgM levels, potentially mediated via an increase in B1a lymphocytes. Although no differences in lesion size were found, transgenic
ApoE-/-APRIL-Tg mice do show potential plaque stabilizing features in advanced atherosclerotic lesions.