152 - B-cell specific CXCR4 protects against atherosclerosis development by controlling plasma IgM levels (ID 1044)
Abstract
Background and Aims
Over the last years, studies focusing on the role of B-cells in atherosclerosis have revealed that this cell subset can have both pro- as well as anti-atherosclerotic properties depending on the specific subset and method of targeting. In this study, the causal role for CXCR4 on B-cells in atherosclerosis development is examined.
Methods
B-cell specific (CD19-Cre) CXCR4 deficient mice on an apolipoprotein E-deficient background were fed an 12 weeks Western diet. Atherosclerotic plaque size and phenotype were analyzed via immunohistochemical and immunofluorescent stainings. Systemic and lymphoid organ leukocyte levels were analyzed using flowcytometry, whereas plasma IgM and cytokine levels were analyzed using cytometric bead array and ELISA, respectively.
Results
We could show that after 12 weeks Western diet feeding, blood and especially bone marrow B1 levels were decreased. This coincided with a striking decrease in plasma IgM levels, while plasma CXCL12 and lipid levels remained unchanged. As expected based on the decreased B1 cell and IgM plasma levels, atherosclerotic lesion size was significantly increased in the aortic root and arch of B-cell specific Cxcr4 deficient mice. Additionally, plaque macrophage content was significantly increased, while smooth muscle cell content, necrotic core and collagen area remained unchanged upon B-cell Cxcr4 deficiency.
Conclusions
Overall, our results clearly suggest a causal role for B-cell CXCR4 in atheroprotection by controlling protective IgM titres, shedding more light onto the complex role of B-cells in atherosclerosis.
