Preeclamptic Placental CD19+ B Cells Are Causal to Hypertension During Pregnancy

BACKGROUND: Patients with preeclampsia exhibit hypertension and chronic inflammation characterized by CD (cluster determinant) 4+T cells, B cells secreting AT1-AA (agonistic autoantibody against the angiotensin II type 1 receptor), inflammatory cytokines, and complement activation. Importantly, a history of COVID-19 during pregnancy is associated with an increased incidence of a preeclampsia-like phenotype and is partly mediated by CD4+T cells. We recently showed pregnant patients with a history of COVID-19 with or without preeclampsia produce AT1-AA, indicating the importance of B lymphocytes in the progression of preeclampsia and possibly of COVID-19. Therefore, we hypothesize that B cells from patients with preeclampsia with or without COVID-19 history induce the preeclampsia phenotype through AT1-AA. METHODS: Placental B cells were isolated from normal pregnant, patients with preeclampsia, normotensive COVID-19 history, or preeclampsia COVID-19 history at delivery. Then, 3×10 5 B cells were transferred intraperitoneally into pregnant athymic rats at gestational day 12. On gestational day 18, carotid catheters were inserted. On gestational day 19, mean arterial pressure was measured, and tissues were collected. RESULTS: Preeclampsia B-cell recipients had significantly increased mean arterial pressure, AT1-AA, inflammatory cytokines, and complement activation compared with normal pregnant B-cell recipients. Recipients of B cells with COVID-19 history had markers of inflammation and hypertension but not to the level of significance as recipients of preeclampsia B cells. Inhibition of AT1-AA attenuated the hypertension that occurred in response to preeclampsia or preeclampsia B cells with COVID-19 history. CONCLUSIONS: This study demonstrates the important role of B cells in contributing to hypertension and chronic inflammation during preeclampsia with or without COVID-19 history through secretion of AT1-AA.