B Lymphocyte-Deficiency in Mice Causes Vascular Dysfunction by Inducing Neutrophilia.

Ning Xia,Andreas Daiber,Rebecca Jung,Thomas Münzel,Susanne Karbach,Ellen I Closs,Jérémy Lagrange,Maximilian Mimmler,Gisela Reifenberg,Philip Wenzel,Alice Habermeier,Huige Li,Solveig Hasselwander,Ari Waisman,Nadine Hövelmeyer

doi:10.3390/biomedicines9111686

Abstract

B lymphocytes have been implicated in the development of insulin resistance, atherosclerosis and certain types of hypertension. In contrast to these studies, which were performed under pathological conditions, the present study provides evidence for the protective effect of B lymphocytes in maintaining vascular homeostasis under physiological conditions. In young mice not exposed to any known risk factors, the lack of B cells led to massive endothelial dysfunction. The vascular dysfunction in B cell-deficient mice was associated with an increased number of neutrophils in the circulating blood. Neutrophil depletion in B cell-deficient mice resulted in the complete normalization of vascular function, indicating a causal role of neutrophilia. Moreover, vascular function in B cell-deficient mice could be restored by adoptive transfer of naive B-1 cells isolated from wild-type mice. Interestingly, B-1 cell transfer also reduced the number of neutrophils in the recipient mice, further supporting the involvement of neutrophils in the vascular pathology caused by B cell-deficiency. In conclusion, we report in the present study the hitherto undescribed role of B lymphocytes in regulating vascular function. B cell dysregulation may represent a crucial mechanism in vascular pathology.

Highlights

Recent studies have implicated B lymphocytes in the pathogenesis of insulin resistance, atherosclerosis and hypertension
B cells are present in the adventitia and in the perivascular adipose tissue of both normal and atherosclerotic arteries [4]
B Cell-Deficiency in Mice Leads to Vascular Dysfunction and Reduced nitric oxide (NO) Production

Summary

Introduction

Recent studies have implicated B lymphocytes in the pathogenesis of insulin resistance, atherosclerosis and hypertension. It has been shown that B cells accumulate in the visceral adipose tissue of diet-induced obese mice. B cell-deficient mice on a high-fat diet are protected from insulin resistance despite weight gain. Transfer of IgG from obese wild-type mice into B cell-deficient mice induces insulin resistance and glucose intolerance [1]. Both the proatherogenic and antiatherogenic effects of B cells have been shown in mouse models of atherosclerosis [2,3]. B cells are present in the adventitia and in the perivascular adipose tissue of both normal and atherosclerotic arteries [4]

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Conclusion