Fetal-maternal immune interaction: blocking antibody and survival of the fetus

Abstract

In the late 1940s it became clear that the homograft reaction was essentially the result of an immune response. Subsequently, Medawar commented on the apparent paradox of the survival of the mammalian fetus in the face of such a potential (cell-mediated) immune response. In an outbred population the fetal-placental unit will be antigenically different to the mother by virtue of its complement of paternal genes and additionally there may be developmental or stage-specific gene products that are immunogenic. Many mechanisms have been proposed to account for the survival of the fetus in the face of a potential immune attack and, while many of these have been investigated in considerable detail, there has been no clear-cut indication that any one plays a predominant role. Either control of immune rejection of the fetus is exercised by an as yet undiscovered mechanism or, more probably, by a combination of some or all of the mechanisms that have been proposed by many workers over the last three decades. Potential controlling processes, which will be reviewed briefly, include: systemic and local modification of maternal responsiveness; altered expression of MHC antigens on extra-embryonic tissues; the placenta as a barrier; and blocking antibody responses. We discuss some of our recent studies in which we have started to look for potential blocking antibodies in a mouse model system. Cells secreting immunoglobulins M and G, characterized in hemolytic plaque assays, have been mapped to areas close to the midgestation mouse embryo, using an immunocryohistological technique. A scaled-down version of hybridoma technology has been used as an analytical probe of the specificity and isotype of immunoglobulin secreted by cells originating either from close to the embryo/fetus or from the para-aortic lymph nodes (PALN). So far monoclonal (IgG1) antibodies with specificity for embryonic cells have been derived together with some monoclonal immunoglobulins with as yet uncharacterized antibody specificity.