Abstract

Arteriogenesis, the growth of pre-existing collateral arteries in response to arterial occlusion, is critically regulated by perivascular immune cells. While innate immune contributions are well-established, the role of B lymphocytes remains poorly understood. We investigated the impact of B cell deficiency on arteriogenesis using B cell-deficient JHT mice in a murine hindlimb model of femoral artery ligation (FAL). Laser-Doppler perfusion imaging, immunofluorescence staining, Giemsa staining, flow cytometry, and differential blood counts were performed at defined time points after FAL. B cell-deficient mice exhibited significantly impaired perfusion recovery on days 3 and 7 post-FAL, accompanied by reduced collateral artery diameter growth and diminished vascular cell proliferation. Early immune analysis revealed elevated platelet–neutrophil aggregate (PNA) formation and increased perivascular mast cell degranulation in B cell-deficient mice despite unchanged circulating cell counts. On day 7, perivascular M2-like macrophage numbers were selectively reduced. Furthermore, B cell deficiency disrupted the temporal reprogramming of γδ T cell subsets, impairing the shift from pro-inflammatory IFN-γ-associated to anti-inflammatory IL-10-associated subpopulations. These findings demonstrate for the first time that B cells are essential coordinators of the sequential innate and regenerative immune response driving productive collateral artery growth, positioning them as potential targets for therapeutic arteriogenesis strategies.

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