B Cell Development Undergoes Profound Changes During Pregnancy

DAMIÁN OSCAR MUZZIO; MAREK ZYGMUNT; FEDERICO JENSEN

Budapest

Congreso; 11th Congress of the European Society For Reproductive Immunology; 2014

Introduction: Mammalian pregnancy represents a challenge to the rules of immunology. The im-mune system must tolerate the growing semi-allogenic fetus at the same time that both, mother and fetus, have to be protected against the threat of pathogens. B cells actively participate in immune responses, mainly through the production of antibodies. Their role in pregnancy is however an issue to be elucidated. Objective: To analyze the impact of gravity on B cells development and function in mice Methods: C57Bl/6 females were allogeneically mated with BALB/c males. B cell populations were analyzed in bone marrow (BM), blood, spleen, para-aortic lymph node (PLN) and peritoneal cavity (PerC) by flow cytometry at early pregnancy (day 7), mid-pregnancy (day 14) and late pregnancy (day 18). Non-pregnant C57Bl/6 females were used as control. Levels of IgM, IgA, IgE and IgG in serum were analyzed by ELISA. Localiza-tion of marginal zone and follicular B cells in the spleen was further analyzed by im-munofluorescence. Results: Pregnancy induced a significant reduction of B lymphopoiesis depicted by a lower number of pre/pro B cells as well as immature B cell in BM of pregnant mice compared to non-pregnant controls. However, mature B cells and plasma cells were accumulated in this tissue during pregnancy indicating B cell activation in the periphery. In keeping with this, higher numbers of marginal zone B cells and antibody producing plasma cells were found in the spleen. Higher titers of IgM, IgA, IgE and IgG found in serum of pregnant mice as compared to non-pregnant control mice clearly confirmed B cell acti-vation during pregnancy. Finally, significantly higher numbers of mature B cells were found in PLN and PerC of pregnant mice as compared to non-pregnant females. Conclusion: We clearly demonstrated in this work that B cell development and function are strongly modified during pregnancy. This piece of information was missing in our understanding of how maternal immune system is adapted to the presence of the semi-allogeneic fetus, hence opening new avenues to be explored.