Intrauterine exposure to HBeAg exerts modest effect on neonatal immune repertoire

The paucity of information on fetal immune repertoire dynamics following intrauterine hepatitis B related antigens exposure precludes elucidation of its effects on fetal immune system.

Totally 34 cord blood (CB) samples from singleton full-term neonates and 29 paired maternal peripheral blood (PB) samples were collected at delivery and divided into four groups based on maternal hepatitis B condition and antiviral intervention history. Clonal information in complementary determining region 3 (CDR3) of T cell receptor β (TCRβ) chain and B cell receptor (BCR) heavy chain encompassing IgM, IgA and IgG heavy chain from all samples were analyzed.

Intrauterine exposure to hepatitis B E antigen (HBeAg) altered preferential selection of some low-frequency V gene segments of TCRβ chain and BCR heavy chain in cord blood. Intrauterine exposure to HBeAg enhanced the coordination between TCRβ chain and IgG heavy chain in cord blood without inducing maturation of BCR heavy chain. Intrauterine exposure to HBeAg reduced similarity of clonal distribution of TCRβ chain in cord blood and reversed by maternal antiviral intervention in late pregnancy, without affecting clonal diversity and evenness of clonal distribution. Intrauterine HBeAg exposure narrowed the divergence in clonal richness, evenness and similarity of clonal distribution of TCRβ chain between cord blood and paired maternal peripheral blood at delivery.

Intrauterine exposure to HBeAg induced clonal expansion of some low-frequency TCRβ clonotypes in parts of cord blood samples, which was reversed by maternal antiviral intervention in late pregnancy.