Thus, these studies suggest that the overall

B cell compartment and its functions are suppressed www.selleckchem.com/products/Tipifarnib(R115777).html partially during normal human pregnancy. The full biological significance of such suppression is unclear, but is believed to enable immune tolerance. Aberrant B cell numbers and functions are associated with obstetric complications [42-59]. Earlier studies have shown that complicated pregnancies exhibit an abnormal increase in the frequencies or absolute numbers of circulating maternal B cells (Table 1). For instance, CD5+ B cell counts are significantly higher in patients with anti-phospholipid syndrome (APS) and recurrent spontaneous abortion (RSA) groups than in healthy controls [43, 45-50]. This B cell subset is also increased in placental tissues of RSA patients [50]. The absolute number and percentages of CD19+ B cells are also increased in pregnancy complications Cabozantinib manufacturer [43, 51-59], and a higher number of CD19+IgD+ B cell numbers are observed in APS mothers with associated risks of thrombotic events [42]. Increases in B cell activation markers and functions have also been reported in pre-eclampsia, intrauterine growth

restriction (IUGR) and pregnancy-induced hypertension (PIH) cases in human studies [52, 58, 60, 61]. Collectively, these studies present the evidence of an association between human pregnancy complications and an abnormal increase in B cell-activated functions and/or numbers. It is not exactly clear what causes these anomalies in the B cell compartment of adverse pregnancies, and whether they simply represent an exacerbation of the pre-existing autoimmune conditions of the mother

that is triggered by the physiological state of pregnancy. Under normal conditions, B lymphopoiesis is suppressed and autoreactive B cells are deleted during pregnancy to maintain maternal–fetal immune tolerance [25-27]. However, these normal regulatory mechanisms are impaired in autoimmunity leading to the expansion of autoreactive B cell subsets and deleterious autoantibody production. This notion is supported strongly by observations of an abnormally increased number of CD19+CD5+, mature CD19+CD27+ and CD19+IgD+ B cells in a number of obstetric conditions (Table 1). Indeed, Olopatadine these B cell subsets are well-known producers of autoantibodies such as rheumatoid factors, anti-thyroid, anti-ssDNA, anti-histone and anti-phospholipid autoantibodies [14, 43, 48, 62-65]. In particular, the autoantibody-producing CD19+CD5+ B cell populations, which possibly include both human B1-like or activated B2 cells, are often expanded in autoimmune conditions such as APS, systemic lupus erythematosus (SLE) and primary Sjögren’s syndrome [43, 65, 66], which are often exacerbated by pregnancy and linked strongly to risks of obstetric complications [9, 10]. Thus, the strong link between CD19+CD5+ B cells and autoimmunity make them a prime candidate for further investigation in pregnancy conditions.