Circulating T_FH (cT_FH) cells express CXCR5, PD‐1, and, when activated, ICOS, and release IL‐21. According to the production of IFN‐γ, IL‐4, and IL‐17 and expression of FoxP3, these cells are also classified as cT_FH1, cT_FH2, cT_FH17, and cT_FR cells, respectively. This CD4⁺T‐cell subset is pivotal to efficient humoral immunity, and pregnancy appears to favor IgG production. Here, not only pregnancy amplified the in vivo production of anti‐HBsAg IgG in HBV immunized women, but the frequency of cT_FH cells was directly correlated with estradiol levels. In vitro, pregnancy‐related dose of 17‐β‐estradiol (E2) directly increased the percentage of different cT_FH subsets. While E2 and progesterone (P4) increased the proportion of differentiated T_FH cells derived from naïve CD4⁺T‐cells, only E2 amplified the release of IL‐21 in those cell cultures. In addition, E2 and P4 increased the proportion of memory B cells and plasma cells, respectively. In SEB‐activated B/T_FH cell co‐cultures, E2, in the presence of P4, increased the production of total IgG. Finally, among the hormones, P4 was stronger in upregulating the percentage of IL‐10⁺T_FR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cT_FH and B cell subsets.

中文翻译：

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人类妊娠水平的雌激素和孕酮通过激活TFH / B细胞轴有助于体液免疫

循环中的T _FH（cT _FH）细胞表达CXCR5，PD-1，并在激活时表达ICOS，并释放IL-21。根据IFN-γ，IL-4和IL-17的产生以及FoxP3的表达，这些细胞也分别分为cT _FH 1，cT _FH 2，cT _FH 17和cT _FR细胞。CD4 ⁺ T细胞亚群对于有效的体液免疫至关重要，而怀孕似乎有利于IgG的产生。在这里，不仅怀孕扩大了在接受HBV免疫的女性体内抗HBsAg IgG的产生，而且还有cT _FH的发生频率细胞与雌二醇水平直接相关。在体外，与妊娠有关的17-β-雌二醇（E2）剂量直接增加了不同的cT _FH亚群的百分比。尽管E2和孕酮（P4）增加了来自原始CD4 ⁺ T细胞的分化型T _FH细胞的比例，但只有E2在那些细胞培养物中扩增了IL-21的释放。此外，E2和P4分别增加了记忆B细胞和浆细胞的比例。在SEB激活的B / T _FH细胞共培养物中，在P4存在下，E2增加了总IgG的产生。最后，在激素中，P4在上调IL-10 ⁺ T _FR的百分比方面更强细胞。总体而言，我们的发现表明E2和P4通过促进不同cT _FH和B细胞亚群的扩增而在体液免疫反应中协同作用。