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

Amy S. Major, Sergio Fazio, MacRae F. Linton

Research output: Contribution to journalArticle

212 Citations (Scopus)

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 -/- 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-γ) and antiatherogenic (interleukin-10 and transforming growth factor-β) cytokine mRNA and a decrease in interleukin-4- and interferon-γ-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.

Original languageEnglish (US)
Pages (from-to)1892-1898
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume22
Issue number11
DOIs
StatePublished - Nov 1 2002
Externally publishedYes

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LDL Receptors
Atherosclerosis
B-Lymphocytes
Interferons
Antibodies
Antigen Presentation
Transforming Growth Factors
Adaptive Immunity
Innate Immunity
Interleukin-4
Interleukin-10
Reverse Transcription
Aorta
Anti-Idiotypic Antibodies
Bone Marrow
Cytokines
Lipids
Polymerase Chain Reaction
Messenger RNA
Enzymes

Keywords

  • Atherosclerosis
  • B cells
  • B-lymphocyte deficiency
  • LDL receptors

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

B-lymphocyte deficiency increases atherosclerosis in LDL receptor-null mice. / Major, Amy S.; Fazio, Sergio; Linton, MacRae F.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 22, No. 11, 01.11.2002, p. 1892-1898.

Research output: Contribution to journalArticle

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AB - 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 -/- 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-γ) and antiatherogenic (interleukin-10 and transforming growth factor-β) cytokine mRNA and a decrease in interleukin-4- and interferon-γ-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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