Endocrine Abstracts

During pregnancy, levels of pregnancy-related proteins and hormones such as progesterone (P4), estrogen, and glucocorticoids (GC) increase. Although the regulatory mechanisms of P4 production in the placenta are not completely understood, studies using mouse models have demonstrated that P4 induces immunosuppression using a GC receptor-dependent pathway, suggesting that both it has been suggested that steroid hormones have a similar effect. Understanding the orchestrated role of P4 and cortisol (COR) is important for understanding the mechanisms of immune regulation during human pregnancy. Based on previous experiments showing that P4-treated T and B cells remained in the spleen, we hypothesized that P4-treated cells could produce functional IgG antibodies. Therefore, we immunized humanized mice and examined antigen-specific antibody production. However, the titer of antiserum in humanized mice varied among individuals and was not significantly different, and the percentage of plasmablasts did not differ between mice treated with P4 and COR. For this, we analyzed the production of antigen-specific B cell clones in mice by preparing hybridomas, treating them with P4 and COR, and analyzing cross-reactivity of whole antibodies to immunizing antigens and third-party antigens. Results showed that spleen cell numbers were lower in COR-treated mice, the entire IgG-secreting clone was maintained in P4-treated mice, and B-cell clones in COR-treated mice were also observed to secrete IgG. In contrast, P4-treated mice produced antigen-specific IgG-secreting clones, slightly fewer than control mice, whereas COR-treated mice did not produce high-titer antigen-specific B cell clones. These results suggest that transient treatment of lymphocytes with high concentrations of P4 preserves the function of humanized murine B cells, whereas treatment of COR significantly reduces function. Few antigen-specific clones per spleen cell were detected in COR-treated mice. The reason may be the low proportion of B cells among CD45+ cells in the spleen. Defects in antigen-specific plasmablast formation may be caused by defects in functional B cell engraftment due to COR pretreatment. Irreversible and systemic humoral immunosuppression has no benefit for immunity during pregnancy. Therefore, to maintain pregnancy, it may be necessary to neutralize the effects of COR with large amounts of P4. Further analysis of the role of P4 and COR during pregnancy would be necessary to understand the immunomodulatory mechanism.