Regulatory B‐Cells Are Associated Negatively With Regulatory T‐Cells and Positively With Cytokines in Peripheral Blood of Pregnant Women

ABSTRACT Problem Regulatory B‐cells (Bregs, CD19 + CD24 hi CD38 hi ) are a specialized B‐cell subset that suppresses immune responses and potentially contribute to the maintenance of an immune‐privileged environment for fetal development during pregnancy. However, little is known about the surrounding immunological environment of Bregs in gestational physiology. The relationship of regulatory T‐cells (Tregs, CD4 + CD25 hi CD127 lo FoxP3 + ) to Bregs in coordinating immunoregulation during pregnancy is unknown. We aimed to determine whether peripheral concentrations of Bregs and/or PD‐L1‐expressing Bregs correlated with Tregs and cytokines during pregnancy. Method Peripheral blood samples were obtained from 29 pregnant women at mean 12 weeks’ gestation. Participants were age ≥ 18, self‐identified as Latina/Hispanic, and N = 12 primigravid. Peripheral blood mononuclear cells were isolated, stained, and analyzed by flow cytometry to determine percentages of Tregs from CD4 + T‐cells and five Treg subsets defined by immune checkpoint markers, and Bregs and PD‐L1 + Bregs from total B‐cells. Levels of 13 cytokines were measured on a Meso Scale Discovery multiplex platform. Results Bregs positively correlated with pro‐inflammatory cytokine interleukin (IL)‐6. PD‐L1 + Bregs positively correlated with T‐cell suppressive cytokine IL‐10. PD‐L1 + Bregs negatively correlated with Tregs and Helios + , CTLA‐4 + , PD‐1 + , TIGIT + , and TIM3 + Tregs. For primigravida, PD‐L1 + Bregs correlated positively with IL‐10 and negatively with Helios + and TIGIT + Tregs. For multigravida, PD‐L1 + Bregs correlated positively with IL‐8 and negatively with Helios + , CTLA‐4 + , PD‐1 + , and TIGIT + Tregs. Conclusions This study provides insight into the immunosuppressive role of Bregs and PD‐L1 + Bregs during human pregnancy. Our results suggest that PD‐L1 + Bregs can employ suppressive mechanisms to limit pro‐inflammatory responses in primigravida.