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M Feldmann

Publications and source records attributed to M Feldmann.

At least 451 records · Page 25Linked to original sources
PubMed1972

Cell interactions in the immune response in vitro. II. The requirement for macrophages in lymphoid cell collaboration.

The requirement for macrophages in thymus-dependent antibody responses was studied in vitro. Three different macrophage-deficient cell populations were studied: spleen cells passed through a glass bead column at 37 degrees C, spleen cells cultured with specific antimacrophage serum, and thoracic duct lymphocytes. These cell populations from mice primed to dinitrophenylated (DNP) fowl gamma globulin were unable to respond to the homologous conjugate in vitro. DNP-reactive B cells were present in normal proportions, since all three macrophage-depleted populations responded normally to macrophage-independent and thymus-independent DNP flagella. Carrier-reactive T cells were present, as the helper capacity of carrier-primed spleen cells was the same as carrier-primed lymphocytes, and thoracic duct lymphocytes are a well-established source of helper cells. The inhibition of the cooperative response was thus due to removal of macrophages, and this was proven by restoration of thymus-dependent anti-DNP responses by small numbers of anti-theta-treated peritoneal exudate cells. These results suggest that macrophages are essential in cell collaboration, While their exact function in cell collaboration is not yet known, the above observation suggests that the mechanism of T-B collaboration involves the surface of macrophages.

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PubMed1972

Induction of immunity and tolerance in vitro by hapten protein conjugates. I. The relationship between the degree of hapten conjugation and the immunogenicity of dinitrophenylated polymerized flagellin.

Of many dinitrophenylated (DNP) protein conjugates tested, only DNP conjugated to polymerized flagellin (DNP-POL) (or the structurally related bacterial flagella) elicited a primary anti-DNP response in vitro. Other DNP proteins, such as DNP-monomeric flagellin (DNP-MON), were capable of inducing secondary responses in vitro. The capacity of DNP-POL to immunize spleen cell suspensions devoid of thymus-derived cells was the reason for the greater immunogenicity of DNP-POL, since even large numbers of flagellin-reactive activated thymus cells did not increase the anti-DNP response of normal spleen cells immunized with DNP-POL, whereas the thymus-dependent response to DNP-MON was markedly increased. The capacity of various batches of DNP-POL to immunize normal spleen cells in vitro varied markedly, depending on the number of DNP groups conjugated. DNP-POL with few DNP groups conjugated was immunogenic, but even at very high concentrations did not induce tolerance. In contrast, highly conjugated DNP-POL did not immunize, but readily induced tolerance. DNP-POL with intermediate degrees of conjugation were, like unconjugated polymeric flagellin, capable of inducing both immunity and tolerance. Since DNP-POL immunizes bone marrow-derived lymphocytes (B cells) directly the reduced response was not due to a masking of carrier determinants, necessary for cell collaboration. By using mixed DNP-5-(dimethylamino)-1-naphthalyl (dansyl)-POL conjugates, it was found that the inhibitory effect of a high degree of hapten conjugated was hapten specific. Depolymerization of DNP-POL to DNP-MON, which does not induce primary anti-DNP responses, was excluded by centrifugation analysis and electron microscopy. The relationship of the degree of hapten conjugation on DNP-POL to the capacity to induce tolerance and immunity in B cells has clarified the mechanism of immunological triggering of these cells. A model of the mechanism of "signal" discrimination between immunity and tolerance in B cells, based on these findings, is proposed.

Animals↗
PubMed1971

The relationship between antigenic structure and the requirement for thymus-derived cells in the immune response.

Certain antigens such as polymerized flagellin are capable of producing relatively normal antibody levels in thymectomized mice, whereas others, including heterologous erythrocytes require the presence of T cells in a helper capacity. The mechanism of thymus-independent antibody production was investigated by comparing the primary IgM responses of spleen cells from ATXBM, XBM, and normal mice to various physical forms of the flagellar antigens of Salmonella adelaide in vitro. No reduction in antibody-forming cell levels to polymerized flagellin over a wide dose range was observed in ATXBM cultures, although the same spleen cells did not respond to an optimal dose of sheep red cells. In contrast, when flagellar determinants were presented in a monomeric form or as flagellin-coated donkey red cells, a highly significant difference was observed between the antibody responses of spleen cells from ATXBM mice and XBM or normal controls. The results suggested that the requirement for T cells in antibody production is not a property of specific antigenic determinants, but depends on the mode of antigenic presentation. The validity of this conclusion was confirmed by using another antigenic determinant (DNP) coupled either to the thymus-independent carrier, POL, or to the thymus-dependent carrier, DRC. Spleen cells from XBM mice produced comparable AFC levels to both forms of DNP, but the results from ATXBM cultures showed a marked difference. The anti-DNP response to DNP-DRC was greatly reduced compared to controls, whereas that to DNP-POL was normal even after prolonged thoracic duct drainage of the ATXBM donors and pretreatment of their spleen cells with anti-theta-serum and complement. The data presented here imply that the role of T cells in humoral immunity is the presentation of antigen to B cells in such a manner as to initiate optimal antibody synthesis.

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