859.3 - The Role of B Cells in Mediating Hypertension in Preeclampsia or COVID-19 Infection During Pregnancy

Owen Herrock (University of Mississippi Medical Center), Lorena Amaral (University of Mississippi Medical Center), Evangeline Deer (University of Mississippi Medical Center), Nathan Campbell (University of Mississippi Medical Center), Sarah Fitzgerald (University of Mississippi Medical Center), Kathy Cockrell (University of Mississippi Medical Center), Babbette LaMarca (University of Mississippi Medical Center)

Preeclampsia (PE), new onset hypertension associated with placental ischemia during pregnancy, is associated with a pro-inflammatory state characterized by increased T Helper cells and B cells secreting agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA). We have previously shown that adoptive transfer of CD4+T cells from PE women causes a PE-like phenotype in immunodeficient (nude athymic) pregnant rats.  Moreover, our lab has shown that depletion of B Cells or inhibition of AT1-AA, a product of B cell activation, attenuates hypertension in various rat models of PE. Interestingly, AT1-AA has been found in patients with COVID-19 (CV) infection. An increase incidence of PE has been associated with a history (hx) of COVID-19 infection during pregnancy. Collectively, this information suggests not only that B cells play an important role in the production of AT1-AA in PE, but also a hx of COVID-19 infection during pregnancy may result in AT1-AA, thereby, contributing to increased risk for PE. Although it is known that B cells are the only producers of antibodies and therefore produce AT1-AA, recent studies have touted that B cells don’t play a role in the hypertension in response to placental ischemia. Current studies have only investigated B cells in animal models of PE; yet, no studies have examined the effects of B cells from PE patients to cause hypertension during pregnancy. We hypothesize that B cells play an important role to cause hypertension and other features of PE during pregnancy and that B cells in COVID hx pregnant patients contribute to AT1-AA in pregnancy. To test this hypothesis, B cells were isolated from the placentas of normal pregnant control (NP), PE, normotensive CV hx, or PE CV hx patients upon delivery. Isolated B cells were transferred i.p. into pregnant Nude Athymic rats at gestation (GD) 12. On GD18 carotid catheters were inserted. Blood pressure (MAP) was measured, pups were weighed, and tissues were collected on GD19. Recipients of placental PE B cells had increased MAP (115±3 mmHg, n=6) compared to recipients of placental NP B cells (100±6 mmHg, n=4, plt;0.05). There were no changes in placental:fetal weight ratio associated with PE B cells (0.42±0.02; n=9) compared to recipients of NP B cells (0.40±0.01, n=6). Also, recipients of placental PE B cells had elevated activated Natural Killer cells in their placentas (33±14, n=3) compared to recipients of NP B cells (24±12, n=2).  Recipients of placental CV Hx PE B cells had elevated MAP (107±7 mmHg, n=2) compared to recipients of placental CV Hx NP B cells (99±8 mmHg, n=3). Animals that received CV hx PE B cells had reduced placental efficiency (0.430, n=1) compared to recipients of CV hx Normotensive B cells (0.38±0.01, n=3). Collectively, this study demonstrates an important role for PE B cells to cause hypertension during pregnancy; and indicates that B cells contribute to a higher incidence of PE in women with a history of COVID-19 infection during pregnancy.

This study was supported by NIH grant RO1HD067541-10 (BL), NIH P20GM121334 (BL,LMA), American heart association (AHA) early career award 19CDA34670055 (LMA), and the Cardiovascular-Renal Research Center Post-doctoral T32 Fellowship: T32HL105324.