Marginal zone B cells are antigenically activated, infiltrate the kidneys, and exacerbate angiotensin II-dependent hypertension in mice

B cells are key contributors to hypertension, but the specific subsets involved and whether their activation is antigen-dependent remain unclear. Here, we show angiotensin II infusion in male and female mice induces hypertension and selectively expands marginal zone B (MZB) cells. Using single-cell multiomic sequencing (RNA+VDJ) and high-dimensional flow cytometry we show MZB cells exhibit increased expression of the antigen-specific activation marker Nur77, undergo clonal expansion, and are enriched for IGHV1 B cell receptor variants. Activated and memory MZB cells also accumulate in the kidneys of hypertensive mice. Importantly, hypertensive responses to angiotensin II infusion were significantly blunted in mice lacking MZB cells (BAFF-R ^-/- ), highlighting a causal role for MZB cells in disease development. These findings identify MZB cells as the major activated B cell subset in hypertension and suggest that targeting MZB cells or the (auto)antigens that activate them may offer a novel approach for treating hypertension.