B2 cells suppress experimental abdominal aortic aneurysms

Am J Pathol. 2014 Nov;184(11):3130-41. doi: 10.1016/j.ajpath.2014.07.006. Epub 2014 Sep 3.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Aorta, Abdominal / metabolism*
  • Aortic Aneurysm, Abdominal / metabolism*
  • B-Lymphocytes / metabolism*
  • Disease Models, Animal
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes, Regulatory / metabolism