IL-10 producing B cells rescue mouse fetuses from inflammation-driven fetal death and are able to modulate T cell immune responses
Mandy Busse, Kim-Norina Jutta Campe, Desiree Nowak, Anne Schumacher, Susanne Plenagl, Stefanie Langwisch, Gisa Tiegs, Annegret Reinhold, Ana Claudia ZenclussenScientific Reports2019
Understanding the mechanisms leading to fetal death following maternal subclinical infections is crucial to develop new therapeutic strategies. Here we addressed the relevance of IL-10 secreting B cells (B10) in the maintenance of the immune balance during gestation. µMT females lacking mature B cells presented normal pregnancies, although their fetuses were smaller and their Treg pool did not expand as in B cell sufficient controls. Pregnant µMT females were more susceptible to LPS despite having less Treg; their fetuses died at doses compatible with pregnancy in WT animals. Adoptive transfer of IL-10 negative B effector cells or B cells from IL-10 deficient mice did not modify this outcome. The transfer of B10 cells or application of recombinant murine IL-10 reduced the fetal loss, associated with a normalization of Treg numbers and cytokine modulation at the feto-maternal interface. B cell-derived IL-10 suppressed the production of IL-17A and IL-6 by T cells and promoted the conversion of naïve cells into Treg. B10 cells are required to restore the immune balance at the feto-maternal interface when perturbed by inflammatory signals. Our data position B cells in a central role in the maintenance of the balance between immunity and tolerance during pregnancy.