B Cells in Preeclampsia; Mediators of Autoantibodies, Endothelial Dysfunction, and Hypertension

Pre-eclampsia (PE), new onset hypertension during pregnancy in association with multi-organ dysfunction, immune activation, agonistic autoantibodies to the angiotensin II type 1 receptor (AT1-AA), and endothelial dysfunction with increased vasoconstrictor endothelin (ET-1). AT1-AA exposure during pregnancy contributes to hypertension, immune activation, and vascular dysfunction by stimulating endothelin-1 during pregnancy. The AT1-AA is produced 7 years postpartum suggesting a memory immune response mediated by memory B cells in the pathophysiology of PE. Although we have shown the role of CD19+ B cells in causing hypertension during pregnancy, the role of CD20+ B cells, a marker expressed on most B cells excluding CD19+ plasma cells but is retained on memory B cells, has not been examined. Thus, we hypothesize that placental CD20+ B cells from PE patients will induce a PE phenotype in pregnant athymic nude rats possibly through AT1-AA stimulated pathways, such as ET-1. The objective of this study was to determine if the adoptive transfer of placental CD20+ B cells isolated from PE women at delivery causes hypertension and endothelial dysfunction via the production of AT1-AA, similarly to CD19+ B cells, in pregnant recipient rats. Three hundred thousand placental CD20+ B cells from normal pregnant (NP) or PE patients were isolated and injected i.p. into nude athymic rats on gestational day (GD) 12. Mini-osmotic pumps containing the AT1-AA activity-blocking peptide, ‘n7AAc’, at a dose of 24 µg/day were inserted on GD 14. On GD 18, carotid catheters were implanted. Mean arterial pressure (MAP) was measured and blood and tissues were collected on GD 19. Renal preproendothelin (PPET) was quantified using Real Time-PCR. AT1-AA was quantified using a cardiomyocyte bioassay. A one-way ANOVA was used for statistical analysis. Participants had similar age, BMI, and gestational age (36±1 (PE) vs 39±0 (NP) weeks) at delivery. PE participants had higher MAP at delivery than controls (p<0.05). MAP was 109±3 mmHg (n=9) in the recipient rats of Normal Pregnant (NP) CD20+ B cells which increased to 123±2 mmHg (n=8, p<0.01) in the recipients of PE B cells. This increase in MAP was lower, 110±3 mmHg (n=6, p<0.05), with ‘n7AAc’. Renal PPET expression increased by 2.60±0.61 fold (ΔΔct) in PE B cell recipients (p<0.05) compared to NP B cell recipients and was significantly lower in ‘n7AAc’ treated rats 0.79±0.15 fold (p<0.01). AT1-AA activity was elevated in the PE B cell recipients (14±2 ΔBPM) compared to NP B cell (1±1 ΔBPM, p<0.01) and was lowered with ‘n7AAc’ (2±3 ΔBPM, p<0.05). CD20+ B cells from placentas of PE women cause hypertension and ET-1 through AT1-AA mediated pathways during pregnancy, thereby supporting an important role for CD20+, possibly memory B cells, in the pathophysiology of PE. This study was supported by NIH grants RO1HL170622 (BL), F31HD110230 (NC), and P20GM121334 (BL). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.