The Role of B Cells in PE Pathophysiology: A Potential Target for Perinatal Cell-Based Therapy?

Abstract

The pathophysiology of preeclampsia (PE) is poorly understood; however, there is a large body of evidence that suggests a role of immune cells in the development of PE. Amongst these, B cells are a dominant element in the pathogenesis of PE, and they have been shown to play an important role in various immune-mediated diseases, both as pro-inflammatory and regulatory cells. Perinatal cells are defined as cells from birth-associated tissues isolated from term placentas and fetal annexes and more specifically from the amniotic membrane, chorionic membrane, chorionic villi, umbilical cord (including Wharton’s jelly), the basal plate, and the amniotic fluid. They have drawn particular attention in recent years due to their ability to modulate several aspects of immunity, making them promising candidates for the prevention and treatment of various immune-mediated diseases. In this review we describe main findings regarding the multifaceted in vitro and in vivo immunomodulatory properties of perinatal cells, with a focus on B lymphocytes. Indeed, we discuss evidence on the ability of perinatal cells to inhibit B cell proliferation, impair B cell differentiation, and promote regulatory B cell formation. Therefore, the findings discussed herein unveil the possibility to modulate B cell activation and function by exploiting perinatal immunomodulatory properties, thus possibly representing a novel therapeutic strategy in PE.

Phenotypic and functional alteration of CD45+ immune cells in the decidua of preeclampsia patients analyzed by mass cytometry (CyTOF)

“…Among these six superclusters, only the proportion of B cells significantly differed between the PE and control groups and was significantly decreased in the PE group, which suggests that B cells may play an important role in the development of PE. Although a few studies on PE conducted two decades ago supported that B cells were involved in PE, recent studies have also gradually pointed out that B cells constitute a dominant element in the pathogenesis of PE; the activation status of B cells may represent a valid therapeutic approach in PE, and B cells have been identified as a target because of their immune modulatory action (28). However, the phenotypic and functional changes of decidual B cells in PE have rarely been explored, and their value in measuring at delivery in the early pathogenesis of PE is unclear.…”

Perspective Chapter: Role of Cytotrophoblast Cells and Placenta-Derived Exosomes in Regulatory B Cell Differentiation and Function during Pregnancy

“…With regard to their multi-faceted roles, B cells may participate in successful pregnancy [11]. A subtype of B cells named Bregs exhibits immunosuppressive function and therefore is considered an important players in immunological tolerance during pregnancy.…”

“…Harnessing Bregs functions may lead to the capacity of using Bregs as an immunotherapeutic agent for averting and treating pregnancy pathologies such as PE. Perinatal cells including cells from term placenta and fetal annexes (amniotic membrane, chorionic membrane, umbilical cord, etc) are able to inhibit B cell proliferation, impair B cell differentiation and promote Bregs formation, frequently due to bioactive factors secreted by perinatal cells [11,143]. These cells are considered as a promising tool for therapeutic approaches in PE [143].…”

“…Recent data has shown that the B cell profile is changed during pregnancy to accommodate the growing fetus [9,10]. Findings have pointed out a crucial role for regulatory B cells (Bregs) in establishing an immunomodulatory (IM) environment relevant for pregnancy [11]. In a steady state, Bregs represent 10% of B cells in peripheral blood, a proportion which increases during pregnancy, with the highest rate being observed in post-partum [12,13].…”

Reproductive Immunology and Pregnancy

“…The next paper also addresses PE pathophysiology. Magatti et al, 2021 [ 15 ] reviewed the role of B cells in immune-mediated conditions, including pregnancy, both as proinflammatory and regulatory cells. They indicate that disruption of the control mechanisms of perinatal cells for the maintenance of normal B-cell function may predispose patients to PE.…”