Abstract 110: B2 Cells Suppress Abdominal Aortic Aneurysms and Increase Peripheral Regulatory T Cells

Abstract

Objective: Recent reports have documented abdominal aortic aneurysm (AA) rupture in patients receiving B cell depletion therapy. This highlights the importance of understanding the role of B cells (B1 and B2 subtypes) in the development of AA. We hypothesized that B2 cells are abundant in AA and aggravate experimental aneurysm formation. Methods: AAs were induced in WT (C57BL/6) mice by elastase perfusion of the abdominal aorta and harvested at 14 days. Aortic B1 and B2 cells were quantified, and, intracellular cytokine synthesis was determined using flow cytometry. Next, AAs were induced in B cell deficient (muMT) mice using either elastase perfusion or topical elastase application to determine the impact of loss of B cells in AA. Finally, adoptive transfer experiments were performed on muMT mice by tail vein injection of 25x10^6 isolated splenic B2 cells or saline. Regulatory T cell (Treg) population was identified as CD4+ T cell expressing Foxp3 (forkhead box P3). Results: B cells appeared in abdominal aortas at day 7 after elastase perfusion in WT mice and persisted at least till day 21. Compared to saline perfused or normal aortas, elastase perfused aortas had greater infiltration of mononuclear cells including B cells (3631±578 in elastase vs 1476±524 in saline, p=0.02) and T cells. B2 cells constituted 93% of total B cells in AA. Furthermore, B cells isolated from elastase and saline perfused aortas displayed high, but similar levels of intracellular IL-6 and IL-10 expression. Interestingly, in both experimental models of AA, muMT mice were prone to AA formation similar to WT mice as evidenced by elastin degradation or infiltration of T cells, neutrophils and macrophages. Contradicting our hypothesis, adoptive transfer of B2 cells suppressed AA formation (102.0±7.3% vs 75.2±5.5%, p=0.01) with concomitant increase in Treg cells in spleen (0.24±0.03% vs 0.92± 0.23%, p=0.02) and aorta (0.37±0.09% vs 1.09±0.38%, p=0.08), and decrease in aortic infiltration of mononuclear cells. Conclusions: Our data suggest that B2 cells constitute the largest population of B cells in experimental AA and participate in protecting aorta from aneurysm formation at least in part by increasing the Treg cell population.