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C M Warner

Publications and source records attributed to C M Warner.

At least 19 recordsLinked to original sources
PubMed1992

Mapping of the SLA complex of miniature swine: mapping of the SLA gene complex by pulsed field gel electrophoresis.

The overall order of the regions of the swine major histocompatibility complex (MHC), the SLA complex, was determined by pulsed field gel electrophoresis (PFGE). It was found that the order of the regions is class II-class III-class I. A class I probe hybridized to a 420 kb Mlu I and a 420 kb Not I fragment as did a class III probe for C2. None of the class II probes hybridized to these fragments. Thus, linkage of class I to class III was shown. The class III C2, Bf, and C4 genes were found to residue in a 190 kb Not I fragment. Linkage of class III and class II genes was shown when both the class III C4 and the class II DR probes hybridized to the same 195 kb Sac II and 340 kb Not I fragments. The class I probe did not hybridize to these fragments. The order of the regions, class II-class III-class I, is similar to that of human MHC genes and may have been conserved in evolution so that coordinated expression of MHC genes could be achieved.

Animals↗
PubMed1992

Removal of Qa-2 antigen alters the Ped gene phenotype of preimplantation mouse embryos.

Embryo survival is influenced by both genetic and environmental factors. Previous research in our laboratory has identified one gene associated with embryonic survival, the Ped gene, a gene that is linked to the major histocompatibility complex (MHC) of the mouse. The Ped gene has been shown to influence the rate of preimplantation embryonic cleavage division, as well as litter size, birth weight, and weaning weight. Genetic mapping of the Ped gene has located it in the Q region of the MHC and has suggested that possible Q region genes encoding the Ped gene are Q3, Q5, Q6, Q7, Q8, and/or Q9. Whereas the protein products of the Q3 and Q5 genes are unknown, the protein product of the very similar Q6, Q7, Q8, and Q9 genes is the Qa-2 antigen. Two forms of membrane-bound Qa-2 antigen are known: glycosylphosphatidylinositol (GPI)-linked and transmembrane bound. Only the GPI-linked form is sensitive to cleavage by phosphatidylinositol phospholipase C (PI-PLC). The first purpose of the present study was to determine the nature of the linkage of the Qa-2 antigen to the cell surface of preimplantation mouse embryos. It was found that all detectable Qa-2 antigen on the embryonic cell surface is sensitive to cleavage by PI-PLC and is therefore bound to the cell membrane by a GPI linkage. Furthermore, removal of Qa-2 antigen from the embryonic cell surface slows down the rate of development of preimplantation mouse embryos. These results suggest the likelihood that the Qa-2 antigen is the Ped gene product.

Animals↗
PubMed1992

Expression of phosphatidylinositol-dependent phospholipase C sensitive Qa-2 antigen is increased on peripheral blood lymphocytes of aging mice.

Qa-2 antigen, a nonclassical MHC antigen, is one of a group of cell surface antigens that may be anchored to the cell surface by a glycophosphatidylinositol (GPI) linkage rather than, as is the case with the classical MHC antigens, K, D, and L, by a transmembrane linkage. Recent studies have shown that T cells may be activated through the cross-linking of GPI anchored Qa-2 antigens by anti-Qa-2 antiserum. The Qa-2 antigens involved in signal transduction in activated T cells are sensitive to lipolytic cleavage by phosphatidylinositol-dependent-phospholipase C (PI-PLC). Since T cell function is known to decline with age, a study was undertaken to determine whether the relative amount of lipase sensitive Qa-2 antigen changes with age. Ficoll- Hypaque purified peripheral blood lymphocytes were obtained from C57BL/6 and A strain mice from 6-30 months of age. The cells were incubated with or without phosphatidylinositol- dependent-phospholipase C followed by incubation with anti-Qa-2 monoclonal antibodies and a fluorescein labeled second antibody. Analysis on a FACScan flow cytometer demonstrated that the A strain mice had a single population of Qa-2 positive lymphocytes which increased in lipase sensitivity with age. The C57BL/6 strain mice of all ages had two populations of Qa-2 positive cells, one staining with high fluorescence intensity (high antigen density) and the other with low fluorescence intensity (low antigen density). The proportion of cells found in the high density peak increased markedly with age, suggesting on overall increase in Qa-2 expression. In young animals, only the high density peak was sensitive to PI-PLC treatment. In older animals, the cells originally appearing in the high density population shifted to the low density population after treatment with PI-PLC, suggesting that there must be both lipase sensitive and lipase insensitive forms of Qa-2 present on lymphocytes in these aging C57BL/6 mice. Overall, these data suggest that the proportion of lymphocytes expressing lipase sensitive Qa-2 is increased on lymphocytes of old mice. Since a role for lipase sensitive GPI-linked Qa-2-antigen has recently been postulated in T cell activation, it is possible that the increased lipase sensitive Qa-2 antigen may play a role in age-related changes in T cell function.

Aging↗
PubMed1978

The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody.

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder x high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.

Animals↗
PubMed1978

Quantitative analysis of spleen cell and immunoglobulin allotype composition of (CBAxCBA/H-T6) in equilibrium C57BL/6 allophenic mice.

Fifteen (CBAxCBA/H-T6) in equilibrium C57BL/6 allophenic mice were analyzed for the parental composition of their spleen white blood cells and serum immunoglobulin allotypes. The spleen compositions, assessed by a microcytotoxicity test, showed that the animals covered a range of parental cell mixtures. The allotype compositions of the IgG2a and IgG2b subclasses were determined by a solid phase radioimmunoassay. Although the absolute amount of IgG2a and IgG2b varied markedly from animal to animal, the percentage of the two allotypes in each subclass was remarkably constant. This suggests that the synthesis of IgG2a and IgG2b may be under a coordinate control system. Also, the spleen cell compositons were in excellent agreement with both the IgG2a and IgG2b subclass compositions. The quantitative analysis of the immune systems of allophenic mice may be first step toward the understanding of the mechanisms of tolerance of histoincompatible cells in allophenic mice.

Animals↗
PubMed1977

Chimeric drift in allophenic mice.

The composition of the immune system of 33 allophenic mice of four different types [C57BL/6 in equilibrium DBA/1, C57BL/6 in equilibrium (CBA X CBA/H-T6), C57BL/6 in equilibrium (A X SJL), DBA/1 in equilibrium (CBA X CBA/H-T6)] was studied. It was found that the parental composition of the peripheral white blood cells changed significantly during a two-month interval in 11/33 or 33% of the mice studied. This phenomenon has been termed chimeric drift. The animals were sacrificed between 9 and 16 months of age, and the parental composition of the peripheral white blood cells, spleen white blood cells, and thymocytes was determined on the day of sacrifice. It was foound that the peripheral white blood cell and spleen white blood cell compositions showed a high degree of correlation. However 8/33 or 24% of the mice studied showed discordance of the spleen and thymocyte cell populations. Seven of the 8 mice which showed spleen-thymocyte discordance, had also shown evidence of chimeric drift earlier in their lives. We suggest that this is evidence that chimeric drift may have an immunological basis.

Animals↗
PubMed1977

The immune response of allophenic mice to the synthetic polymer L-glutamic acid, L-lysine, L-phenylalanine. II. Lack of gene complementation in two nonresponder strains.

The genetic control of the immune response of inbred strains of mice to certain antigens has been demonstrated to be governed by a set of Ir genes linked to the major histocompatibility complex (H-2) of mice (1,2). Until recently, the control was thought to be governed by single, dominant genes, located within the I region of the H-2 complex. Merryman et al. (3) originally demonstrated that the immune response to the synthetic terpolymer L-glutamic acid, L-lysine, L-phenylaline (GLphi) is under dominant, H-2-linked Ir gene control (4-7). This was shown both by crossing two nonresponder parental strains to produce responder offspring in the F(1) generation, and by the analysis of appropriate recombinant stains of mice. The two complementing genes have been mapped in the IA and IC regions of the H-2 complex, and have been termed beta and alpha, respectively (5,6). Thus, any strain of mouse may contain neither, one, or both genes. Only mice containing both genes are capable of responding to GLphi. It has been shown using F(1) hybrid and recombinant strains of mice, that the alpha- and beta-genes can complement each other in either the cis (on the same chromosome) or in the trans (on different chromosomes) position (8). In this paper we report the results of studies aimed at answering the question of whether or not the alpha- and beta- genes can complement each other when they are present in different lymphoid cells. To this end we have constructed allophenic mice composed of two nonresponder strains (A and C57BL/6), which show gene complementation in the F(1) generation. Allophenic mice are chimeras containing two cell types coexisting in a "normal" environment. The mice were tested for the specific cellular composition of the two parental cell types and were found to possess a complete range in the relative proportion of the two cell types. This report demonstrates that regardless of the mixture of cell types present in the allophenic mice, none of them were responders to GLphi. Thus no complementation of the alpha- and beta-genes is seen when the two genes are present in different cells.

Animals↗
PubMed1977

The effect of alpha-amanitin on nucleic acid synthesis in preimplantation mouse embryos.

It has been hypothesized that multiple forms of RNA polymerase may play a role in the control of development and differentiation in eukaryotic organisms. For this to be true, three criteria must be met. First, multiple forms of RNA polymerase must be demonstrated. Second, the relative proportion of the enzyme forms must be shown to change with development or differentiation. And third, the types of RNA synthesized must correlate with the types of RNA polymerase present at each developmental stage. We have previously reported data satisfying the first two criteria for preimplantation mouse embryos. The present paper probes the third criterion in this differentiating system. It was found that although the proportion of the RNA polymerase enzyme forms changes from the 8-cell to the blastocyst stage of development, the types of newly synthesized nucleic acids at each of these stages were similar. Furthermore, inhibition of rRNA, mRNA, and tRNA, by alpha-amanitin, was identical for 8-cell and blastocyst embryos. The only difference between these two stages was that DNA synthesis in blastocysts was more sensitive to inhibition by alpha-amanitin than DNA synthesis in 8-cell embryos. We conclude that the synthesis of different classes of RNA by preimplantation mouse embryos is not simply controlled by changes in the levels of the multiple forms of RNA polymerase.

Amanitins↗
PubMed1977

Chimeric drift in allophenic mice: analysis of changes in red blood cell and white blood cell populations in C57Bl/6 in equilibrium (A X SJL)F1, C57Bl/6 in equilibrium (CBA X CBA/H-T6)F1, and C57Bl/6 in equilibrium DBA/1 mice.

Forty-seven allophenic mice of three different types (C57BL/6 in equilibrium (A X SJL), C57BL/6 in equilibrium (CBA X CBA/H-T6), and C57BL/6 in equilibrium DBA/1) were analyzed for changes in their peripheral white blood cell composition and hemoglobin composition with age. It was found that 10 of the 47 mice showed significant changes termed "chimeric drift" in one or the other or both of these parameters. These 10 mice were classified as unstable chimeras, as opposed to the 37 stable chimeras, which showed no apparent chimeric drift. There was an excellent correlation of peripheral white blood cell and hemoglobin compositions of the stable chimeras. However, the unstable chimeras showed little or no correlation of these two markers. Possible mechanisms of chimeric drift are discussed.

Aging↗