Amy S Major1, Sergio Fazio, MacRae F Linton. 1. Department of Medicine, Division of Cardiovascular Medicine, Vanderbilt University, Nashville, Tenn 37232-6300, USA.
Abstract
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.
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.
Authors: Aleksandar K Stanic; Charles M Stein; Adam C Morgan; Sergio Fazio; MacRae F Linton; Edward K Wakeland; Nancy J Olsen; Amy S Major Journal: Proc Natl Acad Sci U S A Date: 2006-04-24 Impact factor: 11.205
Authors: Emilie K Grasset; Amanda Duhlin; Hanna E Agardh; Olga Ovchinnikova; Thomas Hägglöf; Mattias N Forsell; Gabrielle Paulsson-Berne; Göran K Hansson; Daniel F J Ketelhuth; Mikael C I Karlsson Journal: Proc Natl Acad Sci U S A Date: 2015-04-06 Impact factor: 11.205
Authors: Rima Elhage; Pierre Gourdy; Laurent Brouchet; Jacek Jawien; Marie-José Fouque; Catherine Fiévet; Xavier Huc; Yara Barreira; Jean Claude Couloumiers; Jean-François Arnal; Francis Bayard Journal: Am J Pathol Date: 2004-12 Impact factor: 4.307