This proposal addresses the role of the in utero fetal humoral immune response to the mother's lymphocytes in (a) protection from maternal lymphocytic incursion, (b) possible protection from transmission of maternal viral (HIV) infection, and (c) possible promotion of in utero fetal growth. Studies are aimed at characterizing and quantifying the normal occurrence of fetal/cord B lymphocytes producing IgM reactive with maternal lymphocytes that recognize fetal/paternal histocompatibility antigens. Cord B lymphocytes will be isolated and subjected to limiting dilution such that individual B cell production of immunoglobulin is achieved. The immunoglobulin produced will be purified by affinity chromatography, and its effect on the allogeneic proliferative (MLR) and cytotoxic responses of maternal long term T lymphocytes which recognize fetal/paternal histocompatibility antigens will be assessed. The numbers of B cells secreting immunoglobulin reactive with maternal cells will be determined. Conversely, the numbers of circulating maternal cells with which the immunoglobulin is reactive will be determined. The ability of cord B cells to secrete these specific immunoglobulins will be correlated to their developmental status, i.e., naive or memory, and whether they appear to have been activated in vivo. Studies will be performed on normal pregnancies, high risk pregnancies (especially those in which IUGR is a factor), and those in which the mother is HIV infected. Results of these studies will be relevant to understanding normal pregnancy, the normal development of fetal immunity, and the transmission of HIV infection from mother to fetus or neonate.
NIH ExPorter
NIH ExPorter