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Introduction The pathology of abdominal aortic aneurysm (AAA) is a life-threatening disease, with no treatment able to stop or slow the growth and rupture of AAAs; the only medical option is surgery. A better understanding of the mechanisms triggering this pathology is therefore needed to design new treatments. Immune effectors play a role in the pathology. In particular, it has been shown that IgE antibodies, mast cells (MCs) and germinal center (GC) B cells, which are known to form an axis of the immune system, accumulate in the adventitia of AAA. Objective Our goal is to test if the MC-B cell-IgE axis triggers a local amplification loop that precipitates the rupture of AAAs. Method To assess the effect of MCs on AAA healing in vivo, we created a mouse model that develop aneurysm and can be depleted in MCs. In parallel, we characterized the MC–B cell–IgE axis in blood and arterial samples collected from AAA and control patients. We tested, in vitro, the ability of adventitial soluble molecules, especially IgEs, to activate human MCs. Results We observed that mice which are depleted in MCs during the healing phase of AAA develop smaller aneurysms with elevated collagen density. In human AAA adventitia, MCs are activated, covered by IgEs, and located in the vicinity of GCs, which suggest that they can interact with GC B cells in AAAS. The GC B cells from the adventitia are absent from paired patient blood and some adventitial GC stained positive for IgE. Therefore, adventitial GC probably arise from a local differentiation of B cells and support a local production of IgE. AAA adventitial soluble factors trigger the degranulation of MC and their IgE-dependent production of IL-4, a cytokine required for B cells to produce IgEs (Fig. 1). Conclusion Our data suggest that locally produced IgE directed against lesion-specific antigens activate MCs, which prevent AAA healing and promote the production of more IgEs, leading to an amplification loop of the pathology. [ABSTRACT FROM AUTHOR]