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Angiotensin II synergizes with BAFF to promote atheroprotective regulatory B cells.

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Ponnuswamy, Padmapriya 
Joffre, Jeremie 
Herbin, Olivier 
Esposito, Bruno 
Laurans, Ludivine 


Angiotensin II (AngII) promotes hypertension, atherogenesis, vascular aneurysm and impairs post-ischemic cardiac remodeling through concerted roles on vascular cells, monocytes and T lymphocytes. However, the role of AngII in B lymphocyte responses is largely unexplored. Here, we show that chronic B cell depletion (Baffr deficiency) significantly reduces atherosclerosis in Apoe -/- mice infused with AngII. While adoptive transfer of B cells in Apoe -/- /Baffr -/- mice reversed atheroprotection in the absence of AngII, infusion of AngII in B cell replenished Apoe -/- /Baffr -/- mice unexpectedly prevented the progression of atherosclerosis. Atheroprotection observed in these mice was associated with a significant increase in regulatory CD1dhiCD5+ B cells, which produced high levels of interleukin (IL)-10 (B10 cells). Replenishment of Apoe -/- /Baffr -/- mice with Il10 -/- B cells reversed AngII-induced B cell-dependent atheroprotection, thus highlighting a protective role of IL-10+ regulatory B cells in this setting. Transfer of AngII type 1A receptor deficient (Agtr1a -/-) B cells into Apoe -/- /Baffr -/- mice substantially reduced the production of IL-10 by B cells and prevented the AngII-dependent atheroprotective B cell phenotype. Consistent with the in vivo data, AngII synergized with BAFF to induce IL-10 production by B cells in vitro via AngII type 1A receptor. Our data demonstrate a previously unknown synergy between AngII and BAFF in inducing IL-10 production by B cells, resulting in atheroprotection.



Angiotensin II, Animals, Atherosclerosis, B-Cell Activating Factor, B-Lymphocytes, Regulatory, Biomarkers, Cells, Cultured, Disease Models, Animal, Immunohistochemistry, Interleukin-10, Mice, Mice, Knockout, Phenotype, Receptor, Angiotensin, Type 1

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Springer Science and Business Media LLC
British Heart Foundation (PG/15/76/31756)