B-Cell Deficiency Lowers Blood Pressure in Mice.

The proto-oncogene c-myb (and corresponding nuclear transcription factor, c-Myb) regulates the proliferation and differentiation of hematologic and vascular smooth muscle cells; however, the role of c-Myb in blood pressure regulation is unknown. Here, we show that mice homozygous for a hypomorphic c-myb allele (c-myb(h/h)) conferring reduced c-Myb activity manifest reduced peripheral blood and kidney B220(+) B-cells and have decreased systolic (104 +/- 2 versus 120 +/- 1 mm Hg; P<0.0001) and diastolic blood pressure (71 +/- 2 versus 83 +/- 1 mm Hg; P<0.0001) compared with WT (wild type) mice. Additionally, c-myb(h/h) mice had lower susceptibility to deoxycorticosterone acetate-salt experimental hypertension. Although cardiac (echocardiography) and resistance artery (perfusion myography) functions were normal, metabolic cage studies revealed that c-myb(h/h) mice had increased 24-hour urine output and sodium excretion versus WT. Reconstitution of WT mice with c-myb(h/h) bone marrow transplant and chimeric bone marrow transplant using mice lacking B-cells (J(H)T; h/h>WT and h/h: J(H)T>WT, respectively) decreased blood pressure and increased 24-hour urine output compared with controls (WT>WT; WT:J(H)T>WT). J(H)T mice also had decreased systolic (103 +/- 2 versus 115 +/- 1 mm Hg; P<0.0001) and diastolic blood pressure (71 +/- 2 versus 79 +/- 1; P<0.01) and increased 24-hour urine output versus WT. Real-time quantitative reverse transcription polymerase chain reaction of kidney medulla revealed reduced V2R (vasopressin receptor 2) expression in c-myb(h/h) and J(H)T mice. These data implicate B-cells in the regulation of V2R and its associated effects on salt and water handling and blood pressure homeostasis.