B1a Cell-IgM Axis Protects Against Hypertension by Blunting IFNγ+CD4+T Cells

BACKGROUND: Innate and adaptive immune cells play important roles in the pathogenesis of hypertension. B cells play a crucial role in mammalian adaptive immunity via processing antigens and producing antibodies. However, whether B cells and immunoglobulins are involved in regulating blood pressure in hypertension remains unclear. We aimed to reveal the protective role and the potential immunoregulatory mechanisms of B1a cells in hypertension. METHODS: Wild-type and CD19 knockout (CD19 −/− ) mice received angiotensin II (Ang II) to induce hypertension. Blood pressure measured by radiotelemetry and tail cuff. Vascular damage was assessed by histology and immunofluorescence. Immune cells were analyzed by flow cytometry. Adoptive transfer of different B-cell subsets was performed. In vitro cocultures examined B1a cell effects on CD4+T cells. RESULTS: We found that the frequency of B1a cells was reduced in the blood and peritoneal cavity in wild-type mice after Ang II infusion. We showed that CD19 −/− male mice, which exhibit a marked reduction in B1a cells, largely exacerbated the elevation of both systolic and diastolic blood pressures after Ang II treatment compared with wild type. Vascular dysfunction and damage, including CD4+T cells and macrophage accumulation, aortic structural remodeling, and fibrosis, were worse in CD19 −/− male mice compared with wild-type male mice in response to Ang II. Adoptive transfer of B1a cells, but not B2 cells, protected against Ang II-induced hypertension and vascular damage. The serum level of IgM was reduced in CD19 −/− mice but increased after transferring with B1a cells. In vitro, B1a cells and natural IgM inhibited the activation and IFNγ (interferon gamma) production of CD4+T cells. Furthermore, transferring B1a cells deficient in the secretion of IgM blocked the protective effects in response to Ang II infusion. CONCLUSIONS: Our data demonstrated that B1a cells play a protective role in the development of hypertension via producing natural IgM and inhibiting IFNγ production by CD4+T cells.