Biomedical subjects
Publications and source records attributed to G Urbain-Vansanten.
The author reviews the actual concepts on the mechanisms of self-tolerance. He underlines the complexity and the complementarity of the different phenomenons of clonal deletion, clonal anergy and suppression. In addition, he proposes a new theory on the generation of the immune repertoires based on the presentation of self-antigens by particular antigen-presenting cells, the self-presenting cells.
Preliminary studies on the long-term effects of prenatal and early postnatal irradiation on the immune response to arsonate were performed using A/J mice. Pregnant mice were irradiated (0.5 Gy, X-rays) or sham-irradiated on a single occasion during gestation (between day 5 and 18 post-conception). Alternatively, newborn mice received the same treatment between day 2 and 7 after birth. Mice were immunized with keyhole limpet haemocyanin-arsonate (KLH-Ars) in adjuvant from 2 months after birth. The levels of specific antibodies to arsonate (anti-Ars) were measured by radioimmunoassay. In addition, the Ars-related cross-reactive idiotype (CRIA) was measured by the haemagglutination technique. In the primary response the titre of anti-Ars was reduced in animals that had been irradiated between day 12 and 15 of gestation. In the second response, in contrast, they had increased levels of anti-Ars. After immunization with KLH-Ars, high levels of CRIA were observed in all groups. However, in mice irradiated 18-20 days after conception the level of CRIA was often much higher than the level of anti-Ars, indicating that a large proportion of the CRIA-positive molecules were not specific for Ars. Thus, in this particular case, some specificity of the immune response was lost after irradiation. The expression of recurrent idiotypes may be a sensitive indicator of immunological perturbations after irradiation.
In this paper, we have considered the problem of selection of available repertoires. With Ab2 as immunogens, we have used the idiotypic cascade to explore potential repertoires. Our results suggest that potential idiotypic repertoires are more or less the same within a species or between different species. A given idiotype "à la Oudin" can become a recurrent one within the same outbred species or within different species. Similarly, an intrastrain crossreactive idiotype can be induced in other strains, even though there is a genetic disparity between these strains. The structural basis of this phenomenon has been explored. We next examined results showing the loss and gain of recurrent idiotypes without any intentional idiotypic manipulation. A recurrent idiotype can be lost in a syngeneic transfer and a private one can become recurrent by changing the genetic background. The change of available idiotypic repertoires at the B cell level has profound influences on the idiotypic repertoires of suppressor T cells. All these results imply that idiotypic games are played by the immune system itself, a strong suggestion that the immune system is a functional idiotypic network.
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The LOU/C/Wsl rat inbred strain presents a high incidence of spontaneous malignant ileocecal immunocytomas or monoclonal immunoglobulin-secreting tumors. Some tumors have been transplanted in histocompatible animals over years without any change in their secretion products. Among approximately 600 different monoclonal proteins we have studied so far, we recognized six showing properties different from those of rat IgM, IgA, IgE, or IgG classes, and characteristic of the IgD class.
Taking advantage of recent findings about membrane fluidity, we have studied and compared the biosynthetic capacities of fetal or neonatal mouse B (bone-marrow derived) lymphocytes (until 10 days after birth) and adult B lymphocytes. Although both early and adult lymphocytes can synthesize surface immunoglobulins, they have a different physiological behavior after interaction with a ligand (anti-immunoglobulin sera or antigen), either in vivo or in vitro. Fetal and neonatal lymphocytes bearing surface immunoglobulins do not reexpress their membrane receptors after capping and endocytosis promoted by anti-immunoglobulin sera. On the other hand, adult lymphocytes resynthesize completely their receptors after the same treatment. Furthermore, intrafetal injections of hemocyanin in pregnant mice lead to a striking decrease in the number of hemocyanin-binding cells. It seems plausible that this non-reexpression of surface immunoglobulins could be the first step in tolerance establishment.
Lymphocytes are heterogeneous with respect to their life-span. Typical B cells, bearing on their membranes immunoglobulin receptors, easily detectable by immunofluorescence, belong mainly to the long-lived population: this can be observed using combined autoradiography and immunofluorescence. However, when primed mice receive (-3H) thymidine before a boosting injection of tobacco mosaic virus (TMV), many plasma cells appearing in the spleen during the secondary response are labelled. In irradiated recipients repopulated with spleen cells from donors primed with TMV and injected with tritiated thymidine 2 hours before killing, the majority of plasms cells appearing in the spleen after antigen injection were labelled. If irradiated mice were repopulated simultaneously with spleen cells from donors primed with TMV and injected with (-3H) thymidine, and from donors primed with haemocyanin, most of the anti-TMV plasms cells were labelled, while most of the anti-haemocyanin plasma cells were unlabelled. These results allowed us to exclude non-specific reutilization of labelled thymidine as the main reason of our observations. It is concluded that either plasma cells derive from shortlived precursors or they receive material from a labelled cell able to co-operate specifically with plasma cell precursors.
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Irradiated rabbits grafted with allogeneic lymph node, spleen and bone marrow cells from a donor rabbit hyperimmunized against TMV synthesize high affinity antibodies, displaying mainly recipient allotypic specificities, after antigen boosting. By contrast, recipient rabbits from non-immune donors synthesize antibodies of lower affinity. It is suggested that the differentiation of new emerging host B cells is specifically influenced by the presence of donor-memory cells.
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Irradiated rabbits were grafted with a mixture of bone marrow, lymph node and spleen cells from donors hyperimmunized against TMV. Recipient and donors were characterized by different a allotypic specificities. Antibodies synthesized in the recipients display allotypic markers from the recipients but idiotypic specificities cross-reactive with those of donor antibodies. The results show that the differentiation of new host B cells is influenced by the presence of donor memory cells and are interpreted in the light of network concepts.