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Biomedical subjects

A Coutinho

Publications and source records attributed to A Coutinho.

At least 343 records · Page 19Linked to original sources
PubMed1975

Mechanism of B-cell activation and paralysis by thymus-independent antigens. Additive effects between NNP-LPS and LPS in the specific response to the hapten.

Normal spleen cells showed a bell-shaped dose response profile when stimulated in vitro with the thymus-independent antigen (4-hydroxy-3,5-dinitrophenyl)acetyl (NNP)-lipopolysaccharide (LPS) with regard to the development of high-avidity plaque-forming cells to NNP. The addition of suboptimal concentrations of LPS to cultures stimulated by suboptimal concentrations of NNP-LPS resulted in optimal induction of B cells in that affinity fraction. Addition of LPS to cultures optimally stimulated by NNP-LPS resulted in paralysis of the specific cells. These results are interpreted in terms of the additive effects between the mitogenicity of LPS and the mitogenicity of NNP-LPS, the latter being selectively focused on the specific cells, thus providing further evidence for the 'one nonspecific signal' hypothesis for immune activation of B cells.

Adjuvants, Immunologic↗
PubMed1975

Genetic control of B-cell responses. I. Selective unresponsiveness to lipopolysaccharide.

Spleen cells from C3H/HeJ mice fail to develop both proliferative responses and increased polyclonal antibody secretion in the presence of concentrations of the B-cell mitogen lipopolysaccharide that are optimal for the induction of B-cell responses in conventional strains. This unresponsiveness is selective for lipopolysaccharide, since C3H/HeJ spleen cells respond normally to two other polyclonal B-cell activators-dextran-sulphate and purified protein derivative of tuberculin. These findings are interpreted as indicating a selective defect in the B-cell subpopulation that responds to lipopolysaccharides in conventional strains.

Activation Analysis↗
PubMed1975

Responsiveness of lymphoid precursors to polyclonal B-cell activators.

We have shown previously that in the differentiation of fetal liver cells to mature B cells in irradiated hosts, these cells sequentially gain responsiveness to the polyclonal B-cell activators dextran-sulphate (DxS), lipopolysaccharide (LPS), and purified protein derivative from tuberculin (PPD), in that order. In this paper we show that both fetal liver cells and adult bone marrow cells responded with proliferation to DxS, but not to LPS OR PPD. However, neither fetal liver nor bone marrow cells gave rise to detectable numbers of high-rate antibody-secreting cells on short-term stimulation by polyclonal B-cell activators. The lack of LPS and and PPD responses of fetal liver and bone marrow cells could not be ascribed to the presence of inhibitory cells, and the DxS-induced response in these cell populations was not dependent on adherent cells. However, LPS could inhibit the DxS response of fetal liver cells, possibly indicating that DxS-responsive cells are precursors to B cells. Direct evidence was provided that DxS activated B-cell precursors in bone marrow. Thus, this cell population became responsive to LPS after DxS prestimulation, as measured by DNA synthesis. Bone marrow cells, sequentially stimulated with DxS and LPS, contained increased numbers of cells with surface immunoglobulin, although no significant increase in numbers of antibody-secreting cells was obtained. These data indicate that DxS had the capacity to increase the rate of differentiation of B-cell precursors. Finally, we show that the sequential appearance of responsiveness in B-cell differentiation to polyclonal B-cell activators is not due to lack of accessory cells during early stages in maturation.

Animals↗
PubMed1975

Macrophages suppress direct B-cell activation by lipopolysaccharide.

The influence of macrophages on polyclonal B-cell responses to lipopolysaccharide (LPS) and on a primary, specific immune response to a hapten-LPS conjugate was studied in mouse spleen and lymph node cells in serum-free and serum-supplemented cultures. Macrophages were found not to be necessary, and B cells were directly activated by LPS. In serum-free cultures of macrophage-depleted spleen cells, (a) proliferation and antibody secretion occurred at normal levels or were enhanced when compared with normal spleen cells, (b) the responsiveness of limiting cell numbers to LPS was better than in normal spleen cell cultures, (c) LPS did not increase the number or activate residual macrophages, (d) the primary specific response to a hapten-LPS conjugate developed normally, (e) peripheral lymph node cells, which are known to contain a very low concentration of macrophages, from normal or congenitally athymic (nude) mice mounted excellent proliferative responses to LPS. Furthermore, in cultures supplemented with fetal bovine serum, depletion of adherent cells resulted in enhancement of LPS-induced B-cell responses. Addition of peritoneal macrophages to adherent cell-depleted spleen cells produced suppression at all concentrations of both mitogen and adherent cells. Suppressive activity could also be demonstrated in supernatants from adherent cell cultures stimulated by LPS.

Animals↗
PubMed1975

Continuous growth of mitogen-reactive B lymphocytes.

B-cell mitogens induce continous growth of murine lymphocytes in suspension cultures. Continuous growth is observed only at low cell densitiess, below 10(6) cells/ml, in regularly renewed medium containing beta-mercaptoethanol and a growth-supporting fetal calf serum. Continuous growth of B lymphocytes in culture appears to be favored by conditions under which maturation of Ig-secreting plaque-forming cells does not occur. On the other hand, maturation is observed whenever stimulated B cells cease to divide. This maturation leads to IgM secretion followed by secretion of IgG- or IgD-like molecules. Neither continuous growth of B cells nor the 'switch' to secretion of IgG- or IgD-like molecules requires the presence of T cells.

Animals↗
PubMed1975

Effects of anti-Ia serum on mitogenic responses. I. Inhibition of the proliferative response to B cell mitogen, LPS, by specific anti-Ia sera.

Specific anti-Ia serum in combination with rabbit complement removed the B lymphocyte population normally responsive to LPS mitogenic stimulation. Significant inhibition of this proliferative response was also obtained by brief periods of cell pretreatment with anti-Ia antibodies, but not with specific anti-H-2K antibodies. The population of splenic B cells resistant to anti-Thy-1.2 serum and complement was blocked in a very similar manner by anti-Ia serum, but not by anti-H-2 serum.

Animals↗
PubMed1974

Mechanism of thymus-independent immunocyte triggering. Mitogenic activation of B cells results in specific immune responses.

The present experiments were performed in order to analyze the mechanism by which thymus-independent antigens (nonspecific B-cell mitogens) can induce specific immune responses to antigenic determinants present on the same molecule. The hapten NNP was coupled to the B-cell mitogen, lipopolysaccharide (LPS). The conjugate retained full mitogenic activity and bound specifically to NNP-reactive cells. NNP-LPS activated polyclonal as well as specific anti-NNP antibody synthesis, but the optimal concentrations for induction of specific anti-NNP cells were several orders of magnitude lower than the concentrations required for polyclonal activation. These low concentrations failed to activate nonspecific cells, but they induced specific thymus-independent responses of high-avidity NNP-specific cells with the typical kinetics of antigenic responses in vitro. Furthermore, hapten-specific cells were paralyzed by NNP-LPS concentrations that were optimal for induction of polyclonal activation. Specific activation and paralysis could be abolished by free hapten indicating that selective binding of NNP-LPS to hapten-specific cells was responsible for the specificity of the response. However, the triggering signal lacked specificity, since high-avidity specific anti-NNP cells could still be activated by stimulating concentrations of NNP-LPS in the presence of free hapten, even though the Ig receptor combining sites were presumably occupied by NNP. The findings show that B cells with specific Ig receptors for the antigenic determinants on mitogen molecules preferentially bind these molecules and become activated at concentrations still unsufficient to trigger other B cells that lack specific receptors. It is suggested that activation for primary IgM responses in B cells is the result of "one nonspecific signal." This nonspecific signal is provided by the mitogenic properties of some antigens (highly thymus independent or, alternatively, by nonspecific T-cell factors (for highly T cell-dependent antigens), or both, and the surface structures responsible for triggering are not the Ig receptors. The specific Ig receptors only act as passive focusing devices for nonspecific stimuli, entitling the cell to be selectively activated, even though both the signal and the receptors for the triggering are nonspecific.

Animals↗