European Journal of Immunology

doi: 10.1002/eji.1830100101pmid: N/A

Herzenberg, Leonore A.; Black, Samuel J.; Herzenberg, Leonard A.

doi: 10.1002/eji.1830100102pmid: 6153983

Consideration of the interactions among cells and cell products involved in regulating antibody responses leads us to suggest that such interactions are organized into several discrete circular series (circuits) integrated with one another by virtue of shared circuit components. We see these circuits as individually concerned with particular aspects of regulation (carrier‐specific, idiotype‐specific, etc.), but together constituting an integrated, self‐governing system capable of regulating all aspects of antibody production and assuring the ordedy progress of the response (sequential idiotype representation, affinity maturation, isotype representation, overall or selective non‐ responsiveness, etc.). To illustrate how a circuit‐based regulatory system could be constructed and expected to operate, we describe four integrated circuits here: a core regulatory circuit that determines whether a given idiotype will or will not be produced and three auxiliary regulatory circuits that respond to antigen and serum antibody (idiotype) levels by switching the core regulatory circuit into a suppression or “help” mode. These circuits incorporate the idiotype‐anti‐idiotype recognition system basic to the Jerne network theory but also provide for the operation of other cognitive systems that enable specific interactions between individual circuit elements (B cells, antibody, the various suppressor and helper T cells, macrophages and soluble regulatory products). As an integrated unit, the circuits constitute a detailed “working” model that depends on relatively few assumptions and is consistent with the known interactions between elements and the known properties of responses.

Piguet, Pierre‐François; Vassalli, Pierre

doi: 10.1002/eji.1830100103pmid: 6965911

Athymic nude mice or thymectomized mice, irradiated and reconstituted with T‐ depleted bone marrow cells (“B mice”), were injected with allogeneic or syngeneic thymocytes bearing caryotypically distinct chromosomes. The fate of the thymocytes was investigated after various periods of time using two methods: (a) frequency of the cells bearing the Thy‐1 antigen as detected by immunofluorescence with a heteroantiserum among the recipient spleen cells, (b) presence of chromosomally detectable donor cells in phytohemagglutinin‐stimulated spleen cell cultures. These two methods indicate that allogeneic thymocytes disappear after about 7 days, semiallogeneic thymocytes after about 20 days, while syngeneic thymocytes, even when injected in 50 times lower number (106 cells), are detectable for months, thanks to the sensitivity of the caryotypic method. Allogeneic thymocytes induce the production of high titers of alloantibodies, which were shown to react specifically against their own H‐2, a phenomenon interpreted as a “suicidal” allogeneic collaboration. These experiments demonstrate that the failure of allogeneic thymocytes, in contrast to syngeneic thymocytes, to achieve long‐term restoration of the immune responsiveness of T‐depleted mice is due to a rejection of the foreign thymocytes, and not to a failure of T and B cells to collaborate across the histocompatibility barrier.

Zakin, Mario M.; Boulot, Ginette; Goldberg, Michel E.

doi: 10.1002/eji.1830100104pmid: 6988224

It has been previously reported that a limited proteolysis by trypsin of the β2 subunit of Escherichiiz coli tryptophan synthetase produces a nearly functional dimeric protein, the protomer of which consists of two large, nonoverlapping, polypeptide fragments, F1 and F2. In the study reported here, an immunochemical comparison between the native protein, the nicked protein and its two isolated proteolytic fragments was performed, leading to the following conclusions: (a) The β2 subunit and the nicked protein, regardless of the presence or absence of the coenzyme pyridoxal phosphate and of the reduction of the Schiff base between the cofactor and the protein, are immunologically indistinguishable. This confirms the strong structural similarity between the intact and nicked protein. (b) The failure to detect a change in the immunological reactivity of intact or nicked β2 upon removal or reduction of the coenzyme suggests that pyridoxal phosphate does not play a major role as an antigenic determinant in β2 or in modification of the conformation of the apoprotein. (c) When the two proteolytic fragments are separated, they still cross‐react with native β2, and all the antigenic determinants of β2 are recognized either on isolated Flor on isolated F2 by antibodies directed against native β2. However, the average affinity of the antibodies for the isolated fragments is much lower than for the native or nicked protein. The results are discussed in terms of formation and arrangement of globular intermediates during the folding of the intact protein.

L'age‐Stehr, Johanna; Teichmann, Hans; Gershon, Richard K.; Cantor, Harvey

doi: 10.1002/eji.1830100105pmid: 6965912

An immunoregulatory circuit is described in which B cell blasts activate syngeneic Ly‐1+2−3− T cells to (a) start a reaction which is indistinguishable from a graft‐vs.‐ host reaction (syngeneic GvH) and (b) induce suppressor cell activity which abrogates the syngeneic GvH. Since capping the surface immunoglobulin (Ig) on B cell blasts blocks their ability to activate this circuit, it is likely that the relevant cell surface structure “seen” on the B cell by the Ly‐1 T cell is either Ig itself or another molecule in association with Ig.

Duprez, Veronique; Belucchi, Sylvia; Lévy, Jean Paul

doi: 10.1002/eji.1830100106pmid: 6767612

The generation of cytolytic T lymphocytes (CTL) during the immune response directed against the syngeneic X‐ray‐induced BALB/c RL♂ 1 leukemia has been described previously: T killer cells react with a tumor antigen of RL♂ 1 cells, and the H‐2Dd molecules of the target cells play some role in the interaction. The study of anti‐RL♂ 1 responses of ((C57BL/6 × BALB/c) × BALB/c) mice shows that the major histocompatibility complex controls the anti‐RL♂ 1 CTL reaction at a second level, through an Ir gene, with dominant responsiveness, probably mapping to the right of I‐B and controlling the high or low‐CTL responder phenotype. Another non‐ H‐Associated gene interferes with the H‐2‐linked Ir gene, a responder allele at the non‐H‐2 locus, being necessary for the expression of the high‐responder phenotype at the Ir gene locus.

Koszinowski, Ulrich H.; Gething, Mary‐Jane

doi: 10.1002/eji.1830100107pmid: 6244963

Using noninfectious Sendai virus preparations after selective enzymatic digestion of either of the two viral envelope glycoproteins, it was possible to study the effect of different virion‐cell membrane interactions on virus‐specific cytotoxic T lymphocyte (CTL) induction in vitro. Three different virus preparations having capacity for virus‐ cell fusion, for virus‐cell adsorption or lacking the ability to bind to cell membranes, were all active in the generation of virus‐specific primary and secondary cytotoxic T cells, when added to the culture. Investigations on the responder cell requirements during CTL induction revealed that activation by addition of virions lacking the capacity to bind to cells was sensitive to the depletion of adherent cells. When virions with fusion and binding capacity were presented on tumor stimulator cells, different requirements with respect to adherent cells were obtained in the primary and secondary CTL response to Sendai virus. The data indicate that different viral antigen‐cell membrane interactions govern the activation phase and effector phase of antigen‐ primed T cell populations, while sensitization of unprimed cells is dependent on the presence of adherent, perhaps antigen‐presenting cells.

Wrogemann, Klaus; Weidemann, Maurice J.; Ketelsen, Uwe‐Peter; Wekerle, Hartmut; Fischer, Herbert

doi: 10.1002/eji.1830100108pmid: 6965913

The immediate chemiluminescence (CL) response to concanavalin A (Con A) of rat thymocytes is enhanced 10 to 20‐fold when the cells are preincubated in serum‐free medium for 5–20 h. During this period, multiple encounters between lymphocytes and macrophages occur which morphologically appear as rosettes or grape‐like cell aggregates. Addition of bone marrow‐derived macrophages increases the number of cell aggregates and also the CTL response to Con A. Paradoxically, removal of macrophage‐containing cell aggregates after cocultivation leaves a pure thymocyte population which strongly responds to Con A with CL. Our results confirm that macrophage‐depleted “competent” lymphocytes are capable of CL and, furthermore, that “competence” is gained during cocultivation with macrophages. We are therefore convinced that measurements of macrophage and lymphocyte CL are a powerful tool for further elucidation of lymphocyte differentiation and of interactions between macrophages and lymphocytes.

Degiovanni, Gérard; Cerottini, Jean‐Charles; Brunner, K. Theodor

doi: 10.1002/eji.1830100109pmid: 6153984

The non‐T accessory cell requirement for cytolytic T lymphocyte (CTL) generation in vitro was studied in a system which makes use of particulate membrane preparations as a source of alloantigen, and spleen cells from alloimmune mice as a source of responding cells. It is shown that removal of nylon‐adherent cells from the responding cell population strongly reduced CTL generation, whereas direct removal of Ig+, phagocytic or plastic‐adherent cells had no effect. The CTL response of the nylon‐ nonadherent cell population could be reconstituted by the addition of normal spleen cells, which by themselves do not generate CTL in response to particulate alloantigen. The accessory cell function of normal spleen cells was not affected by depletion of T cells or of phagocytic cells, but was sensitive to γ‐irradiation (1000 rd). The system thus demonstrates the requirement for a nylon‐adherent accessory cell population in the secondary CTL response to particulate alloantigens which does not exhibit the typical characteristics of T cells, B cells or macrophages.

Roberts, Marion M.; Greaves, Melvyn F.

doi: 10.1002/eji.1830100110pmid: 6767613

An antiserum raised against human fetal and childhood thymocytes (anti‐Thy) and absorbed with peripheral lymphocytes (tonsil) detected an antigen(s) shared by thymocytes, T cell‐acute leukemias, activated peripheral T cells and a subset of peripheral T cells. The antigen was expressed by the negative circulating T cell subset after mitogen activation of that separated population. The antigen was shown to be separate from the E rosette receptor, another anti‐T cell serum detected antigen, and β2‐microglobulin; its expression was not related to a particular phase of the cell cycle. The results suggest that the antigen is expressed by T cells only under certain maturational and proliferative conditions.