title: B2 cells suppress experimental abdominal aortic aneurysms.
abstract: Recent reports of rupture in patients with abdominal aortic aneurysm (AAA) receiving B-cell depletion therapy highlight the importance of understanding the role of B cells (B1 and B2 subsets) in the development of AAA. We hypothesized that B2 cells aggravate experimental aneurysm formation. The IHC staining revealed infiltration of B cells in the aorta of wild-type (C57BL/6) mice at day 7 after elastase perfusion and persisted through day 21. Quantification of immune cell types using flow cytometry at day 14 showed significantly greater infiltration of mononuclear cells, including B cells (B2: 93% of total B cells) and T cells in elastase-perfused aortas compared with saline-perfused or normal aortas. muMT (mature B-cell deficient) mice were prone to AAA formation similar to wild-type mice in two different experimental AAA models. Contradicting our hypothesis, adoptive transfer of B2 cells suppressed AAA formation (102.0% ± 7.3% versus 75.2% ± 5.5%; P < 0.05) with concomitant increase in the splenic regulatory T cell (0.24% ± 0.03% versus 0.92% ± 0.23%; P < 0.05) and decrease in aortic infiltration of mononuclear cells. Our data suggest that B2 cells constitute the largest population of B cells in experimental AAA. Furthermore, B2 cells, in the absence of other B-cell subsets, increase splenic regulatory T-cell population and suppress AAA formation.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Akshaya K
authors.initials: AK
authors.lastname: Meher
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: William F
authors.initials: WF
authors.lastname: Johnston
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Guanyi
authors.initials: G
authors.lastname: Lu
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Nicolas H
authors.initials: NH
authors.lastname: Pope
authors.affiliation: Department of Surgery, State University of New York Upstate Medical University, Syracuse, New York.
authors.forename: Castigliano M
authors.initials: CM
authors.lastname: Bhamidipati
authors.affiliation: Robert M. Berne Cardiovascular Research Center, Charlottesville, Virginia.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Harmon
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Gang
authors.initials: G
authors.lastname: Su
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Yunge
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Robert M. Berne Cardiovascular Research Center, Charlottesville, Virginia.
authors.forename: Coleen A
authors.initials: CA
authors.lastname: McNamara
authors.affiliation: Robert M. Berne Cardiovascular Research Center, Charlottesville, Virginia; Division of Vascular and Endovascular Surgery, University of Virginia, Charlottesville, Virginia.
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia; Robert M. Berne Cardiovascular Research Center, Charlottesville, Virginia. Electronic address: gorav@virginia.edu.
authors.forename: Gorav
authors.initials: G
authors.lastname: Ailawadi
mesh_terms: D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism*; D001402:B-Lymphocytes / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism