B-Lymphocyte Deficiency Increases Atherosclerosis in LDL Receptor–Null Mice

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-&ggr;) and antiatherogenic (interleukin-10 and transforming growth factor-&bgr;) cytokine mRNA and a decrease in interleukin-4– and interferon-&ggr;–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.

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