Depletion of B2 but not B1a B cells in BAFF receptor-deficient ApoE-/- mice attenuates atherosclerosis by potently ameliorating arterial inflammation

Tin Soe Kyaw, Christopher Tay, Hamid Hosseini, Peter Kanellakis, Tahlia Gadowski, Fabienne Mackay-Fisson, Peter George Tipping, Alexander Bobik, Ban-Hock Toh

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Abstract

We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE -/- mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE -/- mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R -/- ApoE -/- (BaffR.ApoE DKO) and BAFF-R +/+ApoE -/- (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE -/- mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation
Original languageEnglish
Article numbere29371
Number of pages10
JournalPLoS ONE
Volume7
Issue number1
DOIs
Publication statusPublished - 2012

Cite this

@article{32f1fadefaf44b4db0a4c45c986bb587,
title = "Depletion of B2 but not B1a B cells in BAFF receptor-deficient ApoE-/- mice attenuates atherosclerosis by potently ameliorating arterial inflammation",
abstract = "We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE -/- mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE -/- mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R -/- ApoE -/- (BaffR.ApoE DKO) and BAFF-R +/+ApoE -/- (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82{\%}, 81{\%}, 94{\%}, 72{\%} in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44{\%} and 50{\%} respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE -/- mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation",
author = "Kyaw, {Tin Soe} and Christopher Tay and Hamid Hosseini and Peter Kanellakis and Tahlia Gadowski and Fabienne Mackay-Fisson and Tipping, {Peter George} and Alexander Bobik and Ban-Hock Toh",
year = "2012",
doi = "10.1371/journal.pone.0029371",
language = "English",
volume = "7",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

Depletion of B2 but not B1a B cells in BAFF receptor-deficient ApoE-/- mice attenuates atherosclerosis by potently ameliorating arterial inflammation. / Kyaw, Tin Soe; Tay, Christopher; Hosseini, Hamid; Kanellakis, Peter; Gadowski, Tahlia; Mackay-Fisson, Fabienne; Tipping, Peter George; Bobik, Alexander; Toh, Ban-Hock.

In: PLoS ONE, Vol. 7, No. 1, e29371, 2012.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Depletion of B2 but not B1a B cells in BAFF receptor-deficient ApoE-/- mice attenuates atherosclerosis by potently ameliorating arterial inflammation

AU - Kyaw, Tin Soe

AU - Tay, Christopher

AU - Hosseini, Hamid

AU - Kanellakis, Peter

AU - Gadowski, Tahlia

AU - Mackay-Fisson, Fabienne

AU - Tipping, Peter George

AU - Bobik, Alexander

AU - Toh, Ban-Hock

PY - 2012

Y1 - 2012

N2 - We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE -/- mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE -/- mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R -/- ApoE -/- (BaffR.ApoE DKO) and BAFF-R +/+ApoE -/- (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE -/- mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation

AB - We have recently identified conventional B2 cells as atherogenic and B1a cells as atheroprotective in hypercholesterolemic ApoE -/- mice. Here, we examined the development of atherosclerosis in BAFF-R deficient ApoE -/- mice because B2 cells but not B1a cells are selectively depleted in BAFF-R deficient mice. We fed BAFF-R -/- ApoE -/- (BaffR.ApoE DKO) and BAFF-R +/+ApoE -/- (ApoE KO) mice a high fat diet (HFD) for 8-weeks. B2 cells were significantly reduced by 82%, 81%, 94%, 72% in blood, peritoneal fluid, spleen and peripheral lymph nodes respectively; while B1a cells and non-B lymphocytes were unaffected. Aortic atherosclerotic lesions assessed by oil red-O stained-lipid accumulation and CD68+ macrophage accumulation were decreased by 44% and 50% respectively. B cells were absent in atherosclerotic lesions of BaffR.ApoE DKO mice as were IgG1 and IgG2a immunoglobulins produced by B2 cells, despite low but measurable numbers of B2 cells and IgG1 and IgG2a immunoglobulin concentrations in plasma. Plasma IgM and IgM deposits in atherosclerotic lesions were also reduced. BAFF-R deficiency in ApoE -/- mice was also associated with a reduced expression of VCAM-1 and fewer macrophages, dendritic cells, CD4+ and CD8+ T cell infiltrates and PCNA+ cells in lesions. The expression of proinflammatory cytokines, TNF-α, IL1-β and proinflammatory chemokine MCP-1 was also reduced. Body weight and plasma cholesterols were unaffected in BaffR.ApoE DKO mice. Our data indicate that B2 cells are important contributors to the development of atherosclerosis and that targeting the BAFF-R to specifically reduce atherogenic B2 cell numbers while preserving atheroprotective B1a cell numbers may be a potential therapeutic strategy to reduce atherosclerosis by potently reducing arterial inflammation

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U2 - 10.1371/journal.pone.0029371

DO - 10.1371/journal.pone.0029371

M3 - Article

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JO - PLoS ONE

JF - PLoS ONE

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