LAUSR

Circulating TFH (cTFH) 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 cTFH1, cTFH2, cTFH17, and cTFR 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 cTFH cells was directly correlated with estradiol levels. In vitro, pregnancy‐related dose of 17‐β‐estradiol (E2) directly increased the percentage of different cTFH subsets. While E2 and progesterone (P4) increased the proportion of differentiated TFH 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/TFH 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+TFR cells. Collectively, our findings suggested that E2 and P4 cooperate in the humoral immune response by favoring the expansion of different cTFH and B cell subsets.