B cell activating factor antagonism attenuates the growth of experimental abdominal aortic aneurysm.

B cell activating factor (BAFF), a tumor necrosis factor family of cytokine, was recently identified as a regulator of atherosclerosis, however, its role in aortic aneurysm is not determined. Here, we examined the effect of selective BAFF antagonism using an anti-BAFF antibody (blocks binding of BAFF to receptors BR3, TACI and BCMA) and mBaffR-mFc (blocks binding of BAFF to BR3) 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 the strategies attenuated the formation of AAA. In the intervention group, BAFF antagonism depleted the 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, proinflammatory macrophages and 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 aorta and attenuates the growth of AAA in mice.