B Cell Responses to the Placenta and Fetus

Pregnancy has fascinated immunologists ever since Peter Medawar's observation that reproduction runs contrary to the founding tenets of immunology. During healthy pregnancy, maternal B cells interact with antigens of the foreign conceptus (placenta and fetus) yet do not elicit rejection. Instead, robust, and redundant fetomaternal tolerance pathways generally prevent maternal B cells and antibodies from harming the placenta and fetus. Fetomaternal tolerance is not absolute, and unfortunately there exist several pregnancy complications that arise from breaks therein. Here, important historic and recent developments in the field of fetomaternal tolerance pertaining to maternal B cells and antibodies are reviewed. General rules from which to conceptualize humoral tolerance to the placenta and fetus are proposed. Significant but underexplored ideas are highlighted and topics for future research are suggested, findings from which are predicted to provide insight into the fundamental nature of tolerance and bolster efforts to combat immune-mediated pregnancy complications.