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W D Billington

Publications and source records attributed to W D Billington.

At least 37 records · Page 2Linked to original sources
PubMed1982

Impairment of graft versus host reactivity in pregnant mice.

The popliteal lymph node (PLN) assay for graft versus host (GVH) reactivity has been used to analyse specific features associated with the immunological aspects of the materno-fetal relationship. GVH responses induced following the injection of maternal lymphocytes into F1 hybrid recipients is a particularly relevant model for testing the cellular reactivity of maternal lymphocytes against F1 hybrid determinants since every allogeneic pregnancy could initiate a naturally occurring mother versus F1 allograft reaction. Experiments monitored sequentially the effects of the pregnancy environment and multiparity on maternal cell-mediated immunity. The PLN assay performed within the confines of pregnant F1 hosts indicated that GVH reactivity was significantly suppressed during the mid and late stages of gestation with suppression being greatest in allogeneic combinations. In addition cells obtained from pregnant donors were less efficient than normal cells at GVH induction when transferred to virgin F1 recipients. The suppressive effect was maximal at mid-gestation; however, in this situation, the genotype of the paternal strain had no significant effect on the degree of immunosuppression observed. Multiparity in allogeneic combinations induced anti-paternal humoral immunity but an equivalent increase in GVH reactivity was not detected. These results support the concept of pregnancy-associated suppression of cell-mediated immunity. The nature of the suppressive effect is discussed.

Animals↗
PubMed1981

Humoral immune responses in murine pregnancy. I. Anti-paternal alloantibody levels in maternal serum.

The kinetics and properties of anti-paternal alloantibody produced by female C57BL(H-2b) mice in response to mating with CBA(H-2k) males have been investigated using an immunobead adsorption assay. No alloantibody was ever detected in the first pregnancy or post-partum period. 72% of females exhibited a humoral response in their second pregnancy, detectable from day 16 or 17 post-coitum, and almost all females responded in their third pregnancy. Column chromatographic and immunoelectrophoretic analysis showed that the alloantibody was IgG. Although passive transfer experiments suggested similar stability characteristics to those of cytotoxic antibody induced by experimental hyperimmunization, the pregnancy-induced alloantibody did not exhibit complement-dependent cytotoxicity. The findings are discussed in relation to the nature of the immunogenic stimulus from the conceptus and the regulation and possible function of the humoral immune response in allogeneic pregnancy.

Animals↗
PubMed1981

Expression of serologically detectable H-2 antigens on mid-gestation mouse embryonic tissues.

Mixed haemadsorption assays using antibody-coated indicator sheep erythrocytes and mouse alloantisera revealed that major histocompatibility complex (H-2) antigens were expressed on cells of 24-72 h cultures of mid-gestation mouse embryonic skin, gut, lung, limb-bud and heart but not of embryonic gonad or kidney. The precise time of detection of H-2 antigen expression and the proportions of cells expressing these determinants depended on inbred strain, specific haplotype, tissue of origin and antiserum batch employed. In all tissues the proportion of cells expressing H-2 increased progressively from day 11-12 post-coitum onwards. The findings are discussed with respect to hypotheses concerning the possible role of major histocompatibility antigens in cellular recognition and interactions during embryogenesis.

Animals↗
PubMed1980

Major anti-paternal alloantibody induced by murine pregnancy is non-complement-fixing IgG1.

Maternal humoral responses against antigens of the genetically alien embryo have been reported in several mammalian species, including man, although little is known of the biological relevance of this phenomenon. In the mouse, only females of certain inbred strains mated repeatedly with an allogeneic male produce antibody directed against paternally inherited fetal histocompatibility antigens, as assessed by haemagglutination techniques. It has been suggested that this characteristic of the female is associated with the H-2 haplotype, although some reports indicate that it also extends to other H-2 types. Potentially deleterious complement-dependent cytotoxicity, albeit at low levels, has been claimed to be associated with this alloantibody, but we have been unable to detect any such activity in a large number of maternal sera. Four IgG isotypes (IgG1, IgG2a, IgG2b and IgG3) have been identified and shown to occur in the serum of normal animals. Despite their similar physicochemical properties, which complicate purification procedures, the availability of immunoglobulin-secreting plasmacytomas has made possible the preparation of isotype-specific antisera. Using these antisera in modified haemadsorption assay, we have now demonstrated that the major alloantibody response induced by murine pregnancy involves the non-complement-fixing IgG1 subclass. This is a noncytotoxic antibody with potentially protective (enhancing) properties.

Animals↗
PubMed1979

Macrophage activity in mouse pregnancy.

Antigen handling and clearance by macrophages during mouse pregnancy has been examined by monitoring blood levels of 125I-labelled polyvinyl pryrrolidone (PVP) at different times following its intravenous injection into mated females. PVP clearance is significantly reduced between days 12 and 14 of pregnancy in both syngeneic and allogeneic matings. No significant differences were observed between virgin and mated females at earlier or later states of pregnancy. The findings are discussed in relation to the possible role of macrophages in the immunoregulatory processes involved in the maintenance of the foetus as an intrauterine allograft.

Animals↗
PubMed1978

Major histocompatibility complex and non-major histocompatibility complex antigens on mouse ectoplacental cone and placental trophoblastic cells.

The expression of major histocompatibility complex and non-major histocompatibility complex antigens on mouse trophoblast cultured from two defined stages of development was investigated by the sensitive in vitro mixed haemadsorption assay. Outgrowths obtained 3 to 5 days after explanation of 7 1/2-day ectoplacental cones contained a mixed population of cells. Those with a giant cell morphology showed no haemadsorption with congenic H-2 antisera and were reactive with non H-2 antiserum only in the CBA strain. Other, smaller cells were reactive for both H-2 and non-H-2 in all strains examined except for C57BL, where the cells were nonreactive for H-2. Monolayer cultures of 13 to 14-day placental suspensions tested 24 hr after preparation were strongly reactive for both H-2 and non-H-2. The identity and alloantigenic status of the cells are discussed in relation to their function in maternal-foetal immunological interactions.

Animals↗
PubMed1976

Detection of alloantigens during preimplantation development and early trophoblast differentiation in the mouse by immunoperoxidase labeling.

An immunoperoxidase-labeling technique allowing visualization of antibody binding to the cell surface at the electron microscopical level has been employed an an analysis of H-2 and non-H-2 alloantigen expression on the early mouse embryo. The presence of non-H-2 antigenic determinants has been confirmed on eight-cell, morula, and blastocyst stages of development. Contrary to previous reports, however, low levels of H-2 antigen have also been detected on the blastocyst. This is the earliest stage at which H-2 has been shown to be expressed on the fertilized mouse egg and may reflect the greater resolution of the immunoperoxidase technique. Using two different models to study the critical peri-implantation stages, those of experimentally induced blastocyst activation and blastocyst outgrowth in vitro, it has been demonstrated that antigen loss occurs on the trophectoderm at the time of implantation, and that this is not necessarily dependent upon maternal influence. It is suggested that the loss may be an important factor in the prevention of maternal immune rejection during the establishment of the fetal allograft. The two major components of the early postimplantation conceptus display a striking differential in antigenic status. The embryonic sac shows a high degree of peroxidase labeling, while the ectoplacental cone trophoblast is unlabeled. These findings add support to the concept of antigenic neutrality of the early trophoblast and its role in the maintenance of a normal fetomaternal immunological equilibrium.

Animals↗
PubMed1976

Detection of receptors for immunoglobulin on human placenta by EA rosette formation.

Direct evidence for the existence of Fc receptors on the surface of first trimester and term human placental cells has been obtained by the use of an antibody-coated red cell (EA) rosette assay. The modification of a Ficoll density gradient separation procedure for placental cell population in conjunction with dye uptake experiments, cytocentrifuge preparations and cytological analysis has enabled an identification of the rosette-forming cells in the mature placenta as predominantly, if not entirely, syncytiotrophoblastic. The significance of these findings, together with those demonstrating the presence of cell-surface Fc receptors on the chorionic membrane, are considered in relation to the transmission of immunoglobulin from mother to foetus and to the protection of the foetus as an intra-uterine allograft.

Cell Membrane↗