B Cell-Activating Factor Antagonism Attenuates the Growth of Experimental Abdominal Aortic Aneurysm.
B Cell-Activating Factor Antagonism Attenuates the Growth of Experimental Abdominal Aortic Aneurysm.
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B 细胞激活因子拮抗作用可减弱实验性腹主动脉瘤的生长。
DOI：
10.1016/j.ajpath.2021.08.012
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Meher,AkshayaK
中科院分区：
文献类型：
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作者：
Spinosa,MichaelD;Montgomery,WilliamG;Lempicki,Melissa;Srikakulapu,Prasad;Johnsrude,MatthewJ;McNamara,ColeenA;UpchurchJr,GilbertR;Ailawadi,Gorav;Leitinger,Norbert;Meher,AkshayaK
B 细胞激活因子 (BAFF) 是细胞因子肿瘤坏死因子家族的一部分，最近被确定为动脉粥样硬化的调节因子。然而，其在主动脉瘤中的作用尚未确定。在此，该研究检查了使用抗 BAFF 抗体（阻断 BAFF 与受体 BAFF 受体 3、跨膜激活剂和 CAML 相互作用蛋白以及 B 细胞成熟抗原的结合）和 mBaffR-mFc（阻断 BAFF 与 BAFF 受体 3 的结合）选择性 BAFF 拮抗作用对腹主动脉瘤 (AAA) 小鼠模型的影响。在预防策略中，在诱导AAA之前注射拮抗剂，在干预策略中，在诱导AAA之后注射拮抗剂。两种策略均减弱了 AAA 的形成。在干预组中，BAFF 拮抗作用耗尽了脾脏和循环系统中的大部分成熟 B 细胞亚群，导致 AAA 炎症的消退增强，如 B 细胞和促炎巨噬细胞浸润减少以及凋亡细胞数量减少所示。在 AAA 组织中，B 细胞和巨噬细胞密切接触。在体外，无论是否使用 BAFF 处理，B 细胞都会损害巨噬细胞的胞吞活性，这表明 B 细胞对巨噬细胞功能具有直接的先天作用。总而言之，BAFF 拮抗作用会影响成熟 B 细胞的存活，促进主动脉炎症的消退，并减弱小鼠 AAA 的生长。
B cell–activating factor (BAFF), part of a tumor necrosis factor family of cytokines, was recently identified as a regulator of atherosclerosis; however, its role in aortic aneurysm has not been determined. Here, the study examined the effect of selective BAFF antagonism using an anti-BAFF antibody (blocks binding of BAFF to receptors BAFF receptor 3, transmembrane activator and CAML interactor, and B-cell maturation antigen) and mBaffR-mFc (blocks binding of BAFF to BAFF receptor 3) on a murine model of abdominal aortic aneurysm (AAA). In a prevention strategy, the antagonists were injected before the induction of AAA, and in an intervention strategy, the antagonists were injected after the induction of AAA. Both strategies attenuated the formation of AAA. In the intervention group, BAFF antagonism depleted most of the mature B-cell subsets in spleen and circulation, leading to enhanced resolution of inflammation in AAA as indicated by decreased infiltration of B cells and proinflammatory macrophages and a reduced number of apoptotic cells. In AAA tissues, B cells and macrophages were found in close contact.In vitro, B cells, irrespective of treatment with BAFF, impaired the efferocytosis activity of macrophages, suggesting a direct innate role of B cells on macrophage function. Altogether, BAFF antagonism affects survival of the mature B cells, promotes resolution of inflammation in the aorta, and attenuates the growth of AAA in mice.