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Biomedical subjects

K Mizoguchi

Publications and source records attributed to K Mizoguchi.

At least 127 records · Page 7Linked to original sources
PubMed1984

Ontogeny of the erythrocyte-dependent IgM antibody responses to cell membrane antigens.

Our previous experiments characterized the T-cell independent type 2 B-cell responses to cell membrane antigens that are controlled by two donor cell types with different antigen-presenting (AP) activities. We here report about the ontogeny of this novel type of responses with special reference to the mutual relation of the development among two AP activities and their acceptor functions. The responses of mice to H-2d antigens on allogeneic cells and hapten (fluorescein isothiocyanate) antigens on syngeneic cells were examined in parallel. The positive AP activity displayed by red blood cells (RBC) for induction of anti-hapten responses was fully developed in the fetus, although H-2d antigens on the RBC for induction of anti-H-2d responses was immature in mice under 7 days old. In contrast, the negative AP activity displayed by spleen cells (B cells) for inhibition of the RBC-dependent anti-hapten and anti-H-2d responses was first developed in mice about 3 weeks old. The B cell functions accepting the positive and negative AP activities were also matured by that time. The possible significance of these findings in the physiology and pathology of the unique responses was discussed.

Age Factors↗
PubMed1984

Paradoxical effects of LPS on the T-cell-independent type 2 anti-H-2 alloantigen antibody responses to allogeneic erythrocytes.

Murine allogeneic red blood cells (RBC) induce primary IgM antibody responses to H-2 alloantigens T-cell-independently (TI). In this study we showed that bacterial lipopolysaccharide (LPS), which should activate B lymphocytes polyclonally, could not trigger an anti-H-2d plaque-forming cell response. We then demonstrated that administration of LPS (on days 0-1) with allogeneic RBC suppressed the response of mice to H-2d, while giving LPS 4-6 days after RBC augmented the response. In contrast, LPS did not enable allogeneic spleen cells to induce an anti-H-2d response. Additional experiments showed that the allogeneic RBC behave as a TI class 2 antigen. It was concluded from these results that allogeneic RBC display a peculiar activity that exclusively triggers a TI type-2 B cell response that cannot be initiated by LPS and is modulated by LPS in an abnormal fashion. The possible significance of this finding in the mechanism of occurrence of natural H-2-specific IgM alloantibodies in aged mice is discussed.

Animals↗
PubMed1984

Cellular mechanism of primary anti-Thy-1 antibody responses in vitro induced by uniquely immunogenic thymocyte antigens.

Thy-1 antigens are the only cell membrane antigens known to be able to induce primary antibody responses in vitro. We have shown that antigens from the thymocytes of mice and rats were highly immunogenic in cultures of murine spleen cells for the induction of Thy-1.1-specific plaque-forming cell responses, whereas antigens from other tissues, including brains and bone marrow, were poorly immunogenic, if at all. The thymocyte-specific Thy-1 immunogenicity was carried by disrupted cell membranes, and the specific activity for inducing responses was closely linked to Thy-1. We then tried to determine the mechanism of anti-Thy-1 antibody responses in vitro that were induced by the uniquely immunogenic thymocyte antigens. The thymocyte Thy-1 antigens behaved as T cell-independent class 2 (TI-2) antigens: they induced responses in athymic nude mice but not in CBA/N mice with a B cell defect. The apparent TI-2 responses to thymocyte Thy-1 did, however, require Thy-1+ cells in the responder, similar to anti-DNP-Ficoll responses. The full development of the anti-Thy-1 responses required the participation of splenic adherent cells (SAC). Nevertheless, the mechanism of the SAC dependency of anti-Thy-1 responses did not involve antigen presentation to lymphocytes by antigen-pulsed SAC, which contrasted with the finding that the presentation of antigen by live SAC to lymphocytes was indispensable for responses to DNP-Ficoll. The poor Thy-1 responsiveness of SAC-depleted spleen cells was fully restored by the addition of soluble factors (IL 1-like molecules) released from SAC into the culture, which did not replace the SAC-requirement of responses to DNP-Ficoll. It was concluded from these results that Thy-1 or Thy-1-linked structures on thymocyte membranes have an intrinsic activity to directly signal either TI-2 B cells or immature T cells, or both, for activation in the presence of soluble factors released from adherent accessory cells. This conclusion is discussed in relation to a hypothetical view that the thymocyte Thy-1 would physiologically mediate cell-to-cell interactions among special subsets of lymphocytes under thymic influence.

Animals↗
PubMed1983

High-grade tumor-specific immunity induced by L1210 leukemia variants obtained from the culture of L1210 cells fused with Lesch-Nyhan fibroblasts.

A highly immunogenic variant of the murine L1210 leukemia cell (L1210/LN-1) for generation of tumor immunity has been obtained from culture of L1210 cells originally fused with human Lesch-Nyhan fibroblasts. In L1210/LN-1 cells, no human chromosomes were identified and chromosomes M1 and No. 1 carried by the parent L1210 cells were missing. L1210/LN-1 cells displayed an intermediate morphology between L1210 cells and Lesch-Nyhan fibroblasts. Most of the CDF1 mice that were inoculated with less than 2 X 10(6) L1210/LN-1 cells survived over 60 days without evidence of tumor, whereas the original L1210 cells killed all the mice tested in about 2 weeks. When inoculated with more than 5 X 10(6) L1210/LN-1 cells, CDF1 mice developed tumor. The CDF1 mice which rejected 2 X 10(6) L1210/LN-1 cells were protected very effectively against challenge of otherwise highly aggressive 1-5 X 10(5) L1210 leukemia cells; 40 out of 43 primed mice tested survived for 60 days or longer after the tumor challenge. Even the CDF1 mice primed with irradiated or mitomycin-treated L1210/LN-1 cells survived against a challenge of 10(5) L1210 leukemia cells. They were, however, not protected against P388 leukemia or Meth A sarcoma, indicating that the immunity was specific to L1210 leukemia. The immunity induced by L1210/LN-1 cells was transplantable by immune spleen cells into syngeneic recipients. Thus, the L1210/LN-1 cells we obtained seem to be very useful as an immunogen for generation of high-grade tumor-specific immunity against highly malignant L1210 leukemia.

Animals↗
PubMed1983

Intact and subcellular form of thymocytes of rats are exceptionally immunogenic in mice for inducing anti-Thy-1 T cell-independent class 2 antibody responses.

Results of the present study show that the primary anti-Thy-1.1 antibody response to rat antigen in Thy-1.2 mice is induced exclusively by thymocyte antigen. Thy-1 antigens of brain and bone marrow, which expressed much Thy-1 antigen, were poorly immunogenic if at all. Brain Thy-1 antigen considerably inhibited the immunogenicity of thymocyte Thy-1. Moreover, we found that subcellular form of thymocytes induce as high antibody responses as intact thymocytes do. The subcellular thymocyte Thy-1 antigen behaved as TI-2 antigen, inducing a good response in athymic nude mice but not in CBA/N mice with a B cell defect. The significance of these findings is discussed in relation to the possible physiological activity of Thy-1 or Thy-1-linked molecules on thymocytes specifically mediating lymphocyte differentiation.

Animals↗
PubMed1983

Control of T-cell-dependent antibody responses of mice to rat antigens by donor cell types.

Administration of rat red blood cells (RBC) into mice induced a rat antigen-specific T-cell-dependent primary antibody response that was detected by a plaque assay using rat RBC as a target. This response was not induced by rat thymocytes or rat spleen cells that should share rat-specific antigens with rat RBC. We then demonstrated that rat spleen cells but not rat thymocytes, which were administered with rat RBC, partially inhibit the action of rat RBC for induction of the anti-rat response. This inhibition required live donor FcR+ cells, and seemed to be specific to rat antigens common to RBC and spleen cells. The findings supported the idea that the control by donor cell types, which was originally shown to work for T-cell-independent antibody response [3,5], should be effective for T-cell-dependent response beyond the species barrier.

Animals↗
PubMed1983

Evidence for the erythrocyte as the principal antigenic cell type that triggers primary IgM antibody responses to H-2D alloantigens.

Antigenic requirements for the induction of T cell-independent primary splenic IgM antibody responses (plaque-forming cell responses) to H-2Dd alloantigens were studied. Results show that some functional activity or structural property of the donor cells is required for immunogenicity, because antigens are not active in subcellular forms. An unexpected finding was that allogeneic red blood cells were exceptionally highly immunogenic, and any lymphoid tissues including purified macrophages and tumor cell lines that were not contaminated with red blood cells were virtually nonimmunogenic. The definite role of red blood cells in donor tissues as immunogens was confirmed by water or ammonium chloride treatment that abolished immunogenicity, as well as by phenotyping of the immunogenic cells with antisera. Thus immunogenic cells were positive for erythrocyte-specific and H-2D antigens and negative for Thy-1, Ig, and NK-1. The possible roles of erythrocytes in induction and regulation of transplantation immunity and in B cell activation in general are discussed.

Animals↗
PubMed1982

Control of primary IgM antibody responses to H-2 alloantigens by antigen-bearing live B lymphocytes.

Alloantigen-bearing (H-2d+) peripheral red blood cells, but not red cell-depleted H-2d+ spleen cells, induce primary IgM anti-H-2d plaque-forming cell responses. In this study it is reported that the primary antibody responses to H-2d+ peripheral red blood cells can be markedly suppressed by a subpopulation of H-2d+ spleen cells when they are injected simultaneously or a few days before injection of red blood cells. This suppression was antigen (H-2d)-specific, did not depend on T cells of either the donor or the recipient, and strictly required live donor cells. An energy-dependent action of the donor cell cortex and some proliferation of donor cells in the recipient seemed to be involved in the mechanism of suppression. The donor-suppressor cell type was largely present in the spleen but not in the bone marrow and thymus, and was present in the spleen of athymic nude mice. The suppressor cells displayed the properties of B lymphocytes: they adhered to the nylon wool but not to glass, were of relatively low density (rho less than 1.09), and were surface Ig+, Ia+, Fc receptor-positive but Thy-1-. H-2d+ suppressor-donor B lymphocytes might directly signal to antigen-specific recipient B cells competing with the signal provided by H-2d+ red blood cells for the B cell activation.

Animals↗