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

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 γ-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.

• Authors: Tin Kyaw, Christopher Tay, Abdul Khan, Vanessa Dumouchel, Anh Cao, Kelly To, Merilyn Kehry, Robert Dunn, Alex Agrotis, Peter Tipping, Alex Bobik, Ban-Hock Toh
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 185 Issue 7 Pg. 4410-9 (Oct 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20817865 (Publication Type: Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Murine-Derived
• Rituximab

Topics

• Adoptive Transfer (adverse effects)
• Animals
• Antibodies, Monoclonal (pharmacology)
• Antibodies, Monoclonal, Murine-Derived
• Atherosclerosis (immunology, pathology, therapy)
• B-Lymphocytes (immunology)
• Cell Separation
• Flow Cytometry
• Immunohistochemistry
• Lymphocyte Depletion (methods)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Reverse Transcriptase Polymerase Chain Reaction
• Rituximab