Published online before print September 26, 2002, doi: 10.1161/01.ATV.0000039169.47943.EE
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© 2002 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
B-Lymphocyte Deficiency Increases Atherosclerosis in LDL Receptor–Null Mice
From the Department of Medicine, Division of Cardiovascular Medicine (A.S.M., S.F., M.F.L.), the Department of Pathology (S.F.), and the Department of Pharmacology (M.F.L.), Vanderbilt University, Nashville, Tenn.
Correspondence to any of the authors, Vanderbilt University, Department of Medicine, Division of Cardiovascular Medicine, 2220 Pierce Ave, Room 383, PRB, Nashville, TN 37232-6300. E-mail amy.major,sergio.fazio, or macrae.linton{at}mcmail.vanderbilt.edu
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-
) and antiatherogenic (interleukin-10 and transforming growth factor-ß) cytokine mRNA and a decrease in interleukin-4– and interferon-–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.
Key Words: B-lymphocyte deficiency • B cells • atherosclerosis • LDL receptors
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