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

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. and Deer, E. and Amaral, L.M. and Campbell, N. and Lemon, J. and Ingram, N. and Cornelius, D.C. and Turner, T. and Fitzgerald, S. and Ibrahim, T. and Dechend, R. and 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
Official Publication:	https://doi.org/10.1152/ajprenal.00190.2022
PubMed:	View item in PubMed

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