B2 cells contribute to hypertension and natural killer cell activation possibly via AT1-AA in response to placental ischemia

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Item Type:	Article
Title:	B2 cells contribute to hypertension and natural killer cell activation possibly via AT1-AA in response to placental ischemia
Creators Name:	Herrock, O.T., Deer, E., Amaral, L.M., Campbell, N., Lemon, J., Ingram, N., Cornelius, D.C., Turner, T., Fitzgerald, S., Ibrahim, T., Dechend, R., Wallukat, G. and LaMarca, B.
Abstract:	Preeclampsia, new onset hypertension during pregnancy, is associated with activated T helper cells (Th) and B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). The reduced uterine perfusion pressure (RUPP) model of placental ischemia recapitulates these characteristics. We have shown that Th-B cell communication contributes to AT1-AA and symptoms of preeclampsia in the RUPP rat. B2 cells are classical B cells that communicate with Th cells and are then transformed into memory B cells. We hypothesize that B2 cells cause hypertension, natural killer (NK) cell activation, and complement activation during pregnancy through the production of AT1-AA. To test this hypothesis, total splenic B cells and B2 cells were isolated from normal pregnant (NP) or RUPP rats on gestational day (GD)19 and adoptively transferred into GD12 NP rats. A group of recipient rats was treated with a specific inhibitor peptide of AT1-AA. On GD19, mean arterial pressure was measured, tissues were collected, activated NK cells were measured by flow cytometry, and AT1-AA was measured by cardiomyocyte assay. NP recipients of RUPP B cells or RUPP B2 cells had increased mean arterial pressure, AT1-AA, and circulating activated NK cells compared with recipients of NP B cells. Hypertension in NP recipients of RUPP B cells or RUPP B2 was attenuated with AT1-AA blockade. This study demonstrates that B cells and B2 cells from RUPP rats cause hypertension and increased AT1-AA and NK cell activation in response to placental ischemia during pregnancy. NEW & NOTEWORTHY: This study demonstrates that placental ischemia-stimulated B2 cells induce hypertension and circulating natural killer cell activation and angiotensin II type 1 receptor production in normal pregnant rats.
Keywords:	Preeclampsia, B Cells, Autoantibodies, Animals, Rats
Source:	American Journal of Physiology Renal Physiology
ISSN:	1931-857X
Publisher:	American Physiological Society
Volume:	324
Number:	2
Page Range:	F179-F192
Date:	February 2023
Additional Information:	Copyright © 2023 the American Physiological Society.
Official Publication:	https://doi.org/10.1152/ajprenal.00190.2022
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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