Chronic Placental Ischemia Increases Innate‐like Peritoneal B‐1 B Cells in the Rat
Authors: Regal Jean F , Odean Evan J , Wing Cameron R , Wilcox Jacob A , Gilbert Jeffrey S , Fleming Sherry D 
Published: November 2023

Preeclampsia is characterized by new onset hypertension during pregnancy, reduced placental perfusion, and increased activation of complement, part of the innate immune system. In the reduced uterine perfusion pressure (RUPP) model of placental ischemia‐induced hypertension in the rat, our previous work demonstrated the importance of complement activation, particularly activation products C3a and C5a, in mediating maternal hypertension. In addition, we have demonstrated increased deposition of IgM and complement component C3 in placenta following placenta ischemia suggesting a potential role for natural antibody in complement activation. The innate‐like B‐1 B cells reside and self‐renew in the peritoneum and produce natural antibody that has low affinity for multiple self and non‐self antigens, including apoptotic cells. The natural antibody is generally IgM and/or IgG3 and is produced by B‐1 B cells, but the specific stimuli remain undefined. Prior studies have addressed the importance of the traditional B cell (B‐2 B cell) in placental ischemia‐induced hypertension, but a role for the innate‐like B‐1 B cell is relatively unexplored. We hypothesized that peritoneal B‐1 B cells are important for production of IgM antibody leading to complement activation in placental ischemia induced hypertension. As a first step in testing this hypothesis, we determined if B‐1 B cells increased in peritoneal cavity or spleen following placental ischemia. On gestation day (GD) 14, timed pregnant Sprague Dawley rats underwent either Sham surgery or clip placement on ovarian arteries and abdominal aorta to reduce uterine perfusion pressure (RUPP) resulting in increased maternal blood pressure on GD19. On GD19, mean arterial pressure (MAP) was measured in unanesthetized restrained rats via arterial catheter. As expected, MAP significantly increased (p<0.05) in RUPP (109±3 mmHg, n=5) vs. Sham (93±6 mmHg, n=4). Following measurement of blood pressure, the peritoneal cavity was lavaged with sterile PBS, the spleen removed and mechanically disrupted, and red blood cells lysed. B‐1 B cells (IgM+CD11b+ cells) were enumerated using flow cytometry in both peritoneal lavage and spleen. The B‐1 B cells in the peritoneal cavity significantly increased from 1.64±0.45% in Sham animals to 3.92±0.31% in RUPP animals (p<0.05). The innate‐like B‐1 B cells in spleen were not significantly changed (25.7±4.8 %, RUPP; 27.1±4.2 %, Sham). Concentration of IgM in serum or peritoneal lavage did not significantly change following placental ischemia, though IgM deposition is significantly increased in RUPP vs Sham placenta. Thus, an increase in B‐1 B cells in the peritoneal cavity accompanies placental ischemia induced complement activation and placental IgM deposition. These data suggest that the innate‐like peritoneal B‐1 B cell and natural antibody may be important for increased complement activation in placental ischemia‐induced hypertension.

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NIH HL109843