B2 cells suppress experimental abdominal aortic aneurysms.
B2 cells suppress experimental abdominal aortic aneurysms.
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DOI：
10.1016/j.ajpath.2014.07.006
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
Akshaya K. Meher;W. F. Johnston;G. Lu;Nicolas H. Pope;C. Bhamidipati;Daniel Harmon;Gang Su;Yunge Zhao;C. McNamara;G. Upchurch;G. Ailawadi
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文献类型：
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作者：
Akshaya K. Meher;W. F. Johnston;G. Lu;Nicolas H. Pope;C. Bhamidipati;Daniel Harmon;Gang Su;Yunge Zhao;C. McNamara;G. Upchurch;G. Ailawadi
最近关于接受B细胞去除治疗的腹主动脉瘤(AAA)患者破裂的报道强调了了解B细胞(B1和B2亚群)在AAA发生发展中的作用的重要性。我们推测B2细胞加重了实验性动脉瘤的形成。免疫组织化学染色显示，灌流弹性酶后第7天，野生型(C57BL/6)小鼠的主动脉内有B细胞的浸润，并持续到第21天。第14天用流式细胞仪定量免疫细胞类型显示，与生理盐水灌流或正常主动脉相比，弹性酶灌流的主动脉中单个核细胞的浸润显著增加，包括B细胞(B2：占B细胞总数的93%)和T细胞。在两种不同的实验性AAA模型中，MUMT(成熟B细胞缺陷)小鼠容易形成类似于野生型小鼠的AAA。与我们的假设相反的是，B2细胞过继移植抑制了腹主动脉瘤的形成(102.0%±7.3%比75.2%±5.5%；P<0.05)，同时脾调节性T细胞增加(0.24%±0.03%比0.92%±0.23%；P<0.05)，并减少了单个核细胞对主动脉的侵袭。我们的数据表明，在实验性AAA中，B2细胞构成了最大的B细胞群。此外，B2细胞在缺乏其他B细胞亚群的情况下，增加了脾调节性T细胞的数量，并抑制了AAA的形成。
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.