Obligatory role for B cells in the development of angiotensin II-dependent hypertension

Christopher Te-Lee Chan, Christopher G Sobey, Maggie Lieu, Dorota M Ferens, Michelle M Kett, Henry Diep, Helena Hyun Ah Kim, Shalini M Krishnan, Caitlin V Lewis, Ekaterina Salimova, Peter G Tipping, Antony Vinh, Chrishan S Samuel, Karlheinz Peter, Tomasz J Guzik, Tin S Kyaw, Ban-Hock Toh, Alexander Bobik, Grant R Drummond

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165 Citations (Scopus)


Clinical hypertension is associated with raised serum IgG antibodies. However, whether antibodies are causative agents in hypertension remains unknown. We investigated whether hypertension in mice is associated with B-cell activation and IgG production and moreover whether B-cell/IgG deficiency affords protection against hypertension and vascular remodeling. Angiotensin II (Ang II) infusion (0.7 mg/kg per day; 28 days) was associated with (1) a 25 increase in the proportion of splenic B cells expressing the activation marker CD86, (2) an 80 increase in splenic plasma cell numbers, (3) a 500 increase in circulating IgG, and (4) marked IgG accumulation in the aortic adventitia. In B-cell-activating factor receptor-deficient (BAFF-R-/-) mice, which lack mature B cells, there was no evidence of Ang II-induced increases in serum IgG. Furthermore, the hypertensive response to Ang II was attenuated in BAFF-R-/- (Delta30+/-4 mm Hg) relative to wild-type (Delta41+/-5 mm Hg) mice, and this response was rescued by B-cell transfer. BAFF-R-/- mice displayed reduced IgG accumulation in the aorta, which was associated with 80 fewer aortic macrophages and a 70 reduction in transforming growth factor-beta expression. BAFF-R-/- mice were also protected from Ang II-induced collagen deposition and aortic stiffening (assessed by pulse wave velocity analysis). Finally, like BAFF-R deficiency, pharmacological depletion of B cells with an anti-CD20 antibody attenuated Ang II-induced hypertension by approximately 35 . Hence, these studies demonstrate that B cells/IgGs are crucial for the development of Ang II-induced hypertension and vessel remodeling in mice. Thus, B-cell-targeted therapies-currently used for autoimmune diseases-may hold promise as future treatments for hypertension.
Original languageEnglish
Pages (from-to)1023 - 1033
Number of pages11
Issue number5
Publication statusPublished - 2015

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