The influence of follicular T helper cells to the adaption of B cells during pregnancy

Introduction: Recently, it has been discovered that B cells display several adaptations in terms of maturation and function during pregnancy. Several factors might account for this, including the action of cytokines like IL-21 and cell-cell interactions from Follicular T helper Cells (TfH).

Although the TfH-IL-21-B-Cells pathway has been previously studied in autoimmune diseases, its role in influencing pregnancy outcome has so far not been examined.

Our aim is to deeply characterize the role of TfH-cells in normal and altered pregnancies.

Materials: We used an established mouse model for pregnancy disturbances. CBA/J females were either paired with DBA/2J males, to obtain immune-induced pathological pregnancies, or with BALB/c males, generating normal pregnancies. Non-pregnant mice were used as controls.

Methods: Mice were sacrificed and lymphocytes were isolated from the spleen at day 14 of pregnancy and analyzed by flow cytometry. B cell function was assessed after stimulation with IL-21. Supernatants were frozen for ELISA experiments. Spleen sections were analyzed by immunofluorescence.

Results: Our experiments revealed that the number of TfH decreases in normal pregnancies. In concordance to this, the expression of the IL-21 receptors on B cells was decreased in normal pregnancies compared to disturbed pregnancies. IL-21 addition showed a dual effect on B cell activation and apoptosis which was stimulation-dependent.

Conclusion: Our data suggests that TfH and IL-21 may be relevant factors shaping the B cell responses that allow a healthy pregnancy.