B2 cells suppress experimental abdominal aortic aneurysms

Akshaya K. Meher, William F. Johnston, Guanyi Lu, Nicolas H. Pope, Castigliano Bhamidipati, Daniel B. Harmon, Gang Su, Yunge Zhao, Coleen A. McNamara, Gilbert R. Upchurch, Gorav Ailawadi

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15 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3130-3141
Number of pages12
JournalAmerican Journal of Pathology
Volume184
Issue number11
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Meher, A. K., Johnston, W. F., Lu, G., Pope, N. H., Bhamidipati, C., Harmon, D. B., ... Ailawadi, G. (2014). B2 cells suppress experimental abdominal aortic aneurysms. American Journal of Pathology, 184(11), 3130-3141. https://doi.org/10.1016/j.ajpath.2014.07.006