WEHI Immunology Special Seminar hosted by Dr Hanna Abberger

Dr Hericka Bruna Figueiredo Galvão, MSci(Hons) PhD
Research Officer
 – Centre for Cardiovascular Biology and Disease Research, La Trobe Institute for Molecular Science; Department of Microbiology, Anatomy, Physiology and Pharmacology, School of Agriculture, Biomedicine and Environment  – La Trobe University

Marginal zone B cells – emerging drivers of hypertension

Davis Auditorium

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Including Q&A session

B cells are key contributors to hypertension. They are activated in hypertensive patients, and mice lacking B cells show reduced hypertensive, cardiac and vascular remodeling responses to hypertensive stimuli. However, the specific B cell subsets involved, their mechanism of action and whether their activation is comparable to humans remain poorly understood.

To determine which B cell subsets are activated in murine hypertension and the mechanisms involved, we performed single-cell RNA sequencing and single-cell VDJ sequencing on spleen and bone marrow samples from normotensive and hypertensive mice. Chronic angiotensin II infusion in male and female mice induced hypertension and selectively expanded marginal zone B (MZB) cells, with a concomitant increase in B cell clones and enrichment of IGHV1 B cell receptor variants. Intercellular communication analyses showed increased communication between MZBs and CD8+ T cells in hypertensive mice, with signalling pathways specifically enriched for antigen-presentation. Multiomic sequencing of kidneys from patients with hypertensive chronic kidney disease similarly showed an increase in memory B cells with a MZB phenotype, increased communication with CD8+ T cells and enrichment of antigen-presenting signalling pathways. Spectral flow cytometry of spleens and kidneys from hypertensive mice also showed an increase in MZBs, expression of general (CD69) and antigen-specific (Nur77) activation markers, and memory MZB cell formation. Importantly, hypertensive responses to angiotensin II infusion were significantly blunted in mice lacking MZB cells (BAFF-R-/-).

Our findings identify MZBs as emerging drivers of murine and human hypertension, amplifying adaptive immune responses through antigen-presentation. Targeting of MZB cells or the (auto)antigens that activate them may offer a novel approach for treating hypertension.

Hericka is an early career research officer at the Centre for Cardiovascular Biology & Disease Research, at La Trobe University. She has over 8 years of experience working with preclinical models of cardiovascular disease and her work focuses on understanding how B cells promote hypertension by integrating multiomic computational analyses with traditional research techniques. Hericka’s work with computational analyses have secured >1.7M in funding from the NHMRC, the Australian Centre for AI in Medical Innovation and The CASS Foundation.

All welcome!