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Biomedical subjects

G W Warr

Publications and source records attributed to G W Warr.

At least 91 records · Page 5Linked to original sources

Lymphocyte-like cells of the tunicate, Pyura stolonifera: binding of lectins, morphological and functional studies.

In vitro investigations were carried out to determine whether lymphocyte-like (small round) cells of the tunicate Pyura stolonifera react to allogeneic cells and mitogens in a manner comparable to that of vertebrate immunocytes. The lymphocyte-like cells possessed receptors for concanavalin A, wheat germ agglutinin and soybean lectin as shown by binding of radioiodinated lectins in scintillation counting and autoradiographic assays. This binding did not induce mitogenesis. Mixtures of cells of P. stolonifera individuals taken from the same or distinct localities did not show enhanced DNA synthesis when assayed at time intervals ranging from 3 to 10 days. The small round cells of this and other tunicates are not completely similar to vertebrate lymphocytes in morphology. Our observations support the concept that these cells are not directly homologous to immunologically competent vertebrate lymphocytes, but may serve as haemopoietic stem cells as proposed by other (Endean, 1954; Freeman, 1970).

Animals↗

Use and abuse of sepharose-conjugated antibodies for the isolation of lymphocyte-surface immunoglobulins.

Immunoadsorbents of Sepharose-4B-conjugated antibodies were shown to be suitable for the characterization, by subsequent SDS-polyacrylamide gel electrophoresis, of splenocyte-membrane Immunoglobulin (Ig) solubilized by detergent lysis of surface 125I-labelled cells. However, high non-specific binding of 125I-labelled lymphocyte-membrane components to Sepharose-4B prevented accurate quantition of Ig in such lysates. 125I-labelled lymphocyte-membrane components solubilized by metabolic release also showed high non-specific binding to Sepharose-4B, and this interfered with both quantitative and qualitative analysis of Ig solubilized in this manner. Initial attempts to overcome the nonspecific binding of 125I-labelled lymphocyte-membrane components to Sepharose-4B were unsuccessful, and attention is drawn to the technical problems of using Sepharose-4B as a matrix for solid-phase immunoadsorbent studies of lymphocyte-membrane Ig.

Animals↗

Genetic polymorphism of IgD-like cell surface immunoglobulin in the mouse.

Lymphocyte surface antigens from spleen cells of several mouse strains were studied by cell surface radioiodination, extraction with detergent incubation with various antisera, and separation of complexes using protein A-containing staphylococci as a solid phase adsorbent. Complexes were then dissociated and analyzed by polyacrylamide gel electrophoresis in the presence of sodium diodecyl sulfate. Using this technique and an alloantiserum prepared in C57BL mice against CBA spleen cells, four distinct specific peaks of radioactivity were found with CBA spleen cells. These corresponded to H-2 and Ia antigens, immunoglobulin light chain, and a heavy chain previously proposed to be the murine homolog of the human delta chain. With the same serum, B10.BR spleen cells revealed only H-2 and Ia antigens, whereas C57BL.Ige (allotype congenic) spleen cells showed only the light chain and "delta" chain peaks. Depletion of immunoglobulin from the surface-iodinated preparations resulted in removal of the light chain and "delta" chain peaks. The tissue distribution and membrane expression of this "delta" chain antigen was then studied by indirect immunofluorescence with various C57BL derived alloantisera and lymphoid cells from C57.Ige allotype congenic mice. Significant numbers of positive cells were found in spleen, lymph nodes, and Peyer's patches, whereas few if any positive were found in bone marrow or thymus. No reaction was found between this molecule and alloantisera to any of the previously described immunoglobulin allotypes. It is proposed that these alloantisera to spleen cells recognise one allelic form of the murine "delta" chain coded for by a gene locus closely linked to the known structural genes for mouse immunoglobulin heavy chains. The designation Ig-5 is proposed for this new immunoglobulin heavy chain locus.

Animals↗

Phylogenetic origins of immune recognition: lymphocyte surface immunoglobulins in the goldfish, Carassius auratus.

Membrane immunoglobulin (Ig) of splenocytes and thymocytes of the goldfish, Carassius auratus, was demonstrated by indirect fluorescent-antibody techniques. Observations on shedding and resynthesis indicated that the thymocyte Ig was endogenously produced. The lymphocyte surface proteins were radioiodinated using the lactoperoxidase-catalyzed reaction, and the labeled Ig molecules were isolated by specific precipitation and analyzed by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. The IgM-like membrane Igs of splenocytes and thymocytes were shown to differ in their ease of solubilization with nonionic detergent, and in the sodium dodecyl sulfate/electrophoretic mobility of their heavy chains. The significance of these observations for the evolution of T-cell recognition is discussed.

Animals↗

Heavy chains of murine splenocyte membrane immunoglobulins: a comparison with the heavy chains of human and toad serum immunoglobulins.

The mobilities of murine splenocyte surface immunoglobulin heavy chains were compared by polyacrylamide gel electrophoresis in SDS-containing buffers, with those of the heavy chains of human EgM, IgG, and IgD, and toad IgY. Human zota-chain showed a mobility only slightly faster than that of human mu-chain, and required double-labeling techniques for unequivocal resolution. The mobility of the slower murine splenocyte surface heavy chain was identical to that of human mu-chain, but that of the second splenocyte heavy chain was significantly faster than that of human zota-chain, and similar to that of the heavy chain of toad IgY. Although the second murine splenocyte heavy chain is clearly distinct from mu-chain, no physicochemical evidence exists which relates it directly to human zota-chain.

Animals↗

Evolutionary and developmental aspects of T-cell recognition.

Studies relating to the nature of the antigen-specific T-cell receptor are reviewed in the light of present knowledge of phylogenetic and ontogenetic development. It is suggested that this evidence supports the concept that immunoglobulin (Ig) is the T-cell receptor, and that the following conclusions may be tentatively drawn.

Aging↗

Lymphocyte surface immunoglobulins: detection, characterization, and occurrence in disease of the lymphoid system.

Surface immunoglobulins (Igs) of lymphocytes are of considerable interest because these molecules probably function as receptors for antigen, and knowledge of their molecular properties should provide information on the mechanisms of immune differentiation. The density and types of surface Ig on a cell provide markers useful in indicating the class of a lymphocyte and its stage of maturity. Moreover, knowledge of the specificities of the surface Ig of neoplastic lymphocytes might suggest the nature of agents involved in the generation of the disease. Two broad classes of lymphocytes, bone marrow-derived lymphocytes (B cells) active in antibody secretion, and thymus-derived lymphocytes (T cells) which mediate cellular immune reactions, and their subpopulations must be considered with reference to the nature, origin, and function of their surface immunoglobulin. This article analyzes direct and indirect methods for the demonstration of surface Igs and describes certain physicochemical properties of isolated surface Ig molecules. Roles of these surface molecules in recognition of antigen, initiation of all differentiation, and cooperation among lymphocytes and accessory cells are discussed.

Agammaglobulinemia↗

Effect of Corynebacterium parvum on the class and subclass of antibody produced in the response of different strains of mice to sheep erythrocytes.

Several strains of mice were injected with sheep erythrocytes (SRBC) using C. parvum as adjuvant. The adjuvant effects on the amounts of class and subclass of antibody produced were ranked in the order IgG2b greater than IgG2a and IgM greater than IgG1. In addition, these effects were shown to vary depending on the time of administration of C. parvum relative to antigen. C parvum was shown to have no adjuvant effect on the response of congenitally athymic mice when given at the same time as the antigen, SRBC. On the basis of the reported observations it is suggested that certain of the adjuvant effects of C. parvum require T-cell function.

Adjuvants, Immunologic↗

Effects of oestrogens and pregnancy on the distribution of sheep erythrocytes and the antibody response in mice.

Mice pre-treated with three oestrogenic preparations showed increased hepatic and reduced splenic uptake of 51Cr-labelled sheep erythrocytes (SRBC). The anitbody response to SRBC wahe number of antibody-forming cells in the spleen parallels the amount of SRBC localizing in this organ and that both can be depressed or enhanced by appropriate pre-treatments with oestrogens or colloidal carbon. The effects of these agents are mediated through stimulation or 'blockade' of the phagocytic activity of liver macrophages. Changes in localization of SRBC in pregnant mice were similar to those found after treatment with oestrogens. These changes were, however, rather small and the antibody response of pregnant animals was not affected.

Animals↗

Role of cellular proliferation in the stimulation of MPS phagocytic activity.

Administration of agents such as stilboestrol, endotoxin, C. parvum and zymosan, which enhance the phagocytic activity of the mononuclear phagocyte system, also stimulated cellular proliferation in the liver and spleen as assessed by [13H] thymidine incorporation into these organs, and by autoradiography and the number of mitoses in the liver. Sublethal whole body irradiation abolished the proliferative response to stimulation and also reduced or prevented the increase in phagocytic activity. This latter effect depended on the stimulatory agent used, dose of radiation and time of irradiation with respect to stimulation. The results indicate that cell proliferation is important for the increase in phagocytic activity after administration of C. parvum, zymosan and stilboestrol. Endotoxin, however, appears to act primarily by increasing the capacity of existing cells while at the same time causing cell proliferation. The population of cells responding to zymosan by increased phagocytic activity through proliferation was shown to be resident in the liver.

Animals↗

Haematological changes and iron metabolism in rats after administration of Corynebacterium parvum.

Administration of 1-4 mg of C. parvum to rats caused a transient and mild normochromic and normocytic anaemia with reticulocytosis. There was also an immediate and marked fall of plasma iron concentration and a moderate increase of total iron binding capacity of plasma. Despite increased clearance of 59Fe from the plasma there was no significant change of the plasma iron turnover rate. At later intervals after administration of C. parvum an increased incorporation of iron into red blood cells and the spleen was observed. These changes in iron metabolism have been explained in terms of increased retention of iron in the mononuclear phagocyte system during the first few days after C. parvum and enhanced erythropoiesis at later intervals. Other haematological parameters remained normal, with the exception of the absolute number of lymphocytes, which initially fell sharply but soon returned to, and even exceeded, control levels. Liver and spleen weights increased greatly after administration of C. parvum, reaching a maximum at the end of the first week, and both these organs contained mononuclear cell infiltrates, granulomata and giant cells.

Anemia↗