B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice.

Major AS, Fazio S, Linton MF
Arterioscler Thromb Vasc Biol. 2002 22 (11): 1892-8

PMID: 12426221 · DOI:10.1161/01.atv.0000039169.47943.ee

OBJECTIVE - Atherosclerosis is an inflammatory disease characterized by innate and adaptive immune responses. We investigated the role of B cells and antibodies in the development of atherosclerosis in low density lipoprotein (LDL) receptor-deficient (LDLR(-/-)) mice.

METHODS AND RESULTS - Using wild-type and B cell-deficient mice as bone marrow donors, we were able to generate LDLR(-/-) mice that possessed <1.0% of their normal B cell population. B cell-deficient LDLR(-/-) mice on a Western diet showed marked decreases in total serum antibody and anti-oxidized LDL antibody. B cell deficiency was associated with a 30% to 40% increase in the lesion area in the proximal and distal aortas. Real-time reverse transcription-polymerase chain reaction and enzyme-linked immunospot analyses showed a decrease in proatherogenic (interferon-gamma) and antiatherogenic (interleukin-10 and transforming growth factor-beta) cytokine mRNA and a decrease in interleukin-4- and interferon-gamma-producing cells. Additionally, we observed a decrease in splenocyte proliferation to oxidized LDL in the B cell-deficient LDLR(-/-) mice, suggesting that B lymphocytes may play a role in the presentation of lipid antigen.

CONCLUSIONS - Collectively, these data demonstrate that B cells and/or antibodies are protective against atherosclerosis and that this protection may be conferred by B cell-mediated immune regulation.

MeSH Terms (19)

Animals Antibodies Aorta Arteriosclerosis B-Lymphocytes Cell Division Cholesterol Cytokines Female Lipoproteins, LDL Lymphopenia Mice Mice, Inbred C57BL Mice, Inbred Strains Mice, Mutant Strains Receptors, LDL RNA, Messenger Spleen Triglycerides

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