Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis

Tin Kyaw, Christopher Tay, Abdul Khan, Vanessa Dumouchel, Anh Cao, Kelly To, Merilyn Kehry, Robert Dunn, Alex Agrotis, Peter Tipping, Alexander Bobik, Ban-Hock Toh

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170 Citations (Scopus)

Abstract

Atherosclerosis is a chronic inflammatory arterial disease characterized by focal accumulation of lipid and inflammatory cells. It is the number one cause of deaths in the Western world because of its complications of heart attacks and strokes. Statins are effective in only approximately one third of patients, underscoring the urgent need for additional therapies. B cells that accumulate in atherosclerotic lesions and the aortic adventitia of humans and mice are considered to protect against atherosclerosis development. Unexpectedly, we found that selective B cell depletion in apolipoprotein E-deficient (ApoE(-/-)) mice using a well-characterized mAb to mouse CD20 reduced atherosclerosis development and progression without affecting the hyperlipidemia imposed by a high-fat diet. Adoptive transfer of 5 ?? 10(6) or 5 ?? 10(7) conventional B2 B cells but not 5 ?? 10(6) B1 B cells to a lymphocyte-deficient ApoE(-/-) Rag-2(-/-) common cytokine receptor I?-chain-deficient mouse that was fed a high-fat diet augmented atherosclerosis by 72 . Transfer of 5 ?? 10(6) B2 B cells to an ApoE(-/-) mouse deficient only in B cells aggravated atherosclerosis by >300 . Our findings provide compelling evidence for the hitherto unrecognized proatherogenic role of conventional B2 cells. The data indicate that B2 cells can potently promote atherosclerosis development entirely on their own in the total absence of all other lymphocyte populations. Additionally, these B2 cells can also significantly augment atherosclerosis development in the presence of T cells and all other lymphocyte populations. Our findings raise the prospect of B cell depletion as a therapeutic approach to inhibit atherosclerosis development and progression in humans.
Original languageEnglish
Pages (from-to)4410 - 4419
Number of pages10
JournalJournal of Immunology
Volume185
Issue number7
DOIs
Publication statusPublished - 2010

Cite this

Kyaw, Tin ; Tay, Christopher ; Khan, Abdul ; Dumouchel, Vanessa ; Cao, Anh ; To, Kelly ; Kehry, Merilyn ; Dunn, Robert ; Agrotis, Alex ; Tipping, Peter ; Bobik, Alexander ; Toh, Ban-Hock. / Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis. In: Journal of Immunology. 2010 ; Vol. 185, No. 7. pp. 4410 - 4419.
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abstract = "Atherosclerosis is a chronic inflammatory arterial disease characterized by focal accumulation of lipid and inflammatory cells. It is the number one cause of deaths in the Western world because of its complications of heart attacks and strokes. Statins are effective in only approximately one third of patients, underscoring the urgent need for additional therapies. B cells that accumulate in atherosclerotic lesions and the aortic adventitia of humans and mice are considered to protect against atherosclerosis development. Unexpectedly, we found that selective B cell depletion in apolipoprotein E-deficient (ApoE(-/-)) mice using a well-characterized mAb to mouse CD20 reduced atherosclerosis development and progression without affecting the hyperlipidemia imposed by a high-fat diet. Adoptive transfer of 5 ?? 10(6) or 5 ?? 10(7) conventional B2 B cells but not 5 ?? 10(6) B1 B cells to a lymphocyte-deficient ApoE(-/-) Rag-2(-/-) common cytokine receptor I?-chain-deficient mouse that was fed a high-fat diet augmented atherosclerosis by 72 . Transfer of 5 ?? 10(6) B2 B cells to an ApoE(-/-) mouse deficient only in B cells aggravated atherosclerosis by >300 . Our findings provide compelling evidence for the hitherto unrecognized proatherogenic role of conventional B2 cells. The data indicate that B2 cells can potently promote atherosclerosis development entirely on their own in the total absence of all other lymphocyte populations. Additionally, these B2 cells can also significantly augment atherosclerosis development in the presence of T cells and all other lymphocyte populations. Our findings raise the prospect of B cell depletion as a therapeutic approach to inhibit atherosclerosis development and progression in humans.",
author = "Tin Kyaw and Christopher Tay and Abdul Khan and Vanessa Dumouchel and Anh Cao and Kelly To and Merilyn Kehry and Robert Dunn and Alex Agrotis and Peter Tipping and Alexander Bobik and Ban-Hock Toh",
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Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis. / Kyaw, Tin; Tay, Christopher; Khan, Abdul; Dumouchel, Vanessa; Cao, Anh; To, Kelly; Kehry, Merilyn; Dunn, Robert; Agrotis, Alex; Tipping, Peter; Bobik, Alexander; Toh, Ban-Hock.

In: Journal of Immunology, Vol. 185, No. 7, 2010, p. 4410 - 4419.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Conventional B2 B cell depletion ameliorates whereas its adoptive transfer aggravates atherosclerosis

AU - Kyaw, Tin

AU - Tay, Christopher

AU - Khan, Abdul

AU - Dumouchel, Vanessa

AU - Cao, Anh

AU - To, Kelly

AU - Kehry, Merilyn

AU - Dunn, Robert

AU - Agrotis, Alex

AU - Tipping, Peter

AU - Bobik, Alexander

AU - Toh, Ban-Hock

PY - 2010

Y1 - 2010

N2 - Atherosclerosis is a chronic inflammatory arterial disease characterized by focal accumulation of lipid and inflammatory cells. It is the number one cause of deaths in the Western world because of its complications of heart attacks and strokes. Statins are effective in only approximately one third of patients, underscoring the urgent need for additional therapies. B cells that accumulate in atherosclerotic lesions and the aortic adventitia of humans and mice are considered to protect against atherosclerosis development. Unexpectedly, we found that selective B cell depletion in apolipoprotein E-deficient (ApoE(-/-)) mice using a well-characterized mAb to mouse CD20 reduced atherosclerosis development and progression without affecting the hyperlipidemia imposed by a high-fat diet. Adoptive transfer of 5 ?? 10(6) or 5 ?? 10(7) conventional B2 B cells but not 5 ?? 10(6) B1 B cells to a lymphocyte-deficient ApoE(-/-) Rag-2(-/-) common cytokine receptor I?-chain-deficient mouse that was fed a high-fat diet augmented atherosclerosis by 72 . Transfer of 5 ?? 10(6) B2 B cells to an ApoE(-/-) mouse deficient only in B cells aggravated atherosclerosis by >300 . Our findings provide compelling evidence for the hitherto unrecognized proatherogenic role of conventional B2 cells. The data indicate that B2 cells can potently promote atherosclerosis development entirely on their own in the total absence of all other lymphocyte populations. Additionally, these B2 cells can also significantly augment atherosclerosis development in the presence of T cells and all other lymphocyte populations. Our findings raise the prospect of B cell depletion as a therapeutic approach to inhibit atherosclerosis development and progression in humans.

AB - Atherosclerosis is a chronic inflammatory arterial disease characterized by focal accumulation of lipid and inflammatory cells. It is the number one cause of deaths in the Western world because of its complications of heart attacks and strokes. Statins are effective in only approximately one third of patients, underscoring the urgent need for additional therapies. B cells that accumulate in atherosclerotic lesions and the aortic adventitia of humans and mice are considered to protect against atherosclerosis development. Unexpectedly, we found that selective B cell depletion in apolipoprotein E-deficient (ApoE(-/-)) mice using a well-characterized mAb to mouse CD20 reduced atherosclerosis development and progression without affecting the hyperlipidemia imposed by a high-fat diet. Adoptive transfer of 5 ?? 10(6) or 5 ?? 10(7) conventional B2 B cells but not 5 ?? 10(6) B1 B cells to a lymphocyte-deficient ApoE(-/-) Rag-2(-/-) common cytokine receptor I?-chain-deficient mouse that was fed a high-fat diet augmented atherosclerosis by 72 . Transfer of 5 ?? 10(6) B2 B cells to an ApoE(-/-) mouse deficient only in B cells aggravated atherosclerosis by >300 . Our findings provide compelling evidence for the hitherto unrecognized proatherogenic role of conventional B2 cells. The data indicate that B2 cells can potently promote atherosclerosis development entirely on their own in the total absence of all other lymphocyte populations. Additionally, these B2 cells can also significantly augment atherosclerosis development in the presence of T cells and all other lymphocyte populations. Our findings raise the prospect of B cell depletion as a therapeutic approach to inhibit atherosclerosis development and progression in humans.

UR - http://www.jimmunol.org/content/early/2010/09/03/jimmunol.1000033.full.pdf

U2 - 10.4049/jimmunol.1000033

DO - 10.4049/jimmunol.1000033

M3 - Article

VL - 185

SP - 4410

EP - 4419

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -