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Biomedical subjects

D E Mosier

Publications and source records attributed to D E Mosier.

At least 127 records · Page 7Linked to original sources
PubMed1976

In vitro responses of CBA/N mice: spleen cells of mice with an X-linked defect that precludes immune responses to several thymus-independent antigens can respond to TNP-lipopolysaccharide.

Spleen cells from CBA/N mice with an X-linked B cell defect were examined for their ability to form antibody in vitro after stimulation with the T-independent antigen TNP-LPS. In contradistinction to their failure to respond to some conventional T-independent antigens such as type III pneumococcal polysaccharide or DNP-AECM-Ficoll, spleen cells from (CBA/N X DBA/2)F1 male mice were able to make a specific anti-TNP PFC response after culture with TNP-LPS. Their response differed from that of phenotypically normal (CBA/N X DBA/2)F1 female littermate spleen cells in that more TNP-LPS was required to elicit the peak anti-TNP response and the anti-TNP antibody secreted by F1 male cells was of lower avidity than that of F1 female cells. The polyclonal antibody response to unsubstituted LPS did not differ substantially between normal and defective B cells. Tnymus-derived cells were not required for the TNP-LPS response by either F1 male or female cells. We conclude that CBA/NB cells can respond to certain T-independent antigens that are able either to induce a very strong activating signal upon ligand-surface receptor interaction and/or to stimulate immature B cells (with a characteristic high surfact immunoglobulin profile) which fail to respond to antigens like DNP-AECM-Ficoll.

Animals↗
PubMed1975

Ontogeny of mouse lymphocyte function. II. Development of the ability to produce antibody is modulated by T lymphocytes.

The relative functional maturity of neonatal mouse spleen T- and B-cell populations was assessed by comparing the ability to respond to the thymic-independent antigen, DNP-Ficoll, or thymic-dependent SRBC by producing antibody in vitro. Although mouse spleen cells responded to DNP-Ficoll at an earlier age than they responded to SRBC or TNP-SRBC, the reason for the lag in the T-dependent response was confounded by the finding of high numbers of suppressor T lymphocytes in the neonatal spleen. Thus, small numbers of neonatal spleen T cells or thymocytes significantly decreased the in vitro antibody response of adult spleen cells. Although B lymphocytes appear to be functionally mature soon after birth, their acitivity may be modulated by an excess of suppressor T cells; e.g., the reconstitution of helper cell function in the neonatal spleen required anti-theta treatment before addition of adult helper cells. Suppressive activity attributable to T cells seems to play a dominant role in determining the ability of the neonatal animal to react positively or negatively to antigenic stimulation.

Age Factors↗
PubMed1975

Ontogeny of mouse T-lymphocyte function.

The development of lymphocytes within the fetal and neonatal BALB/c mouse thymus is reviewed with particular emphasis on the maturity of immunologic functions. Fetal thymocytes respond by vigorous proliferation to stimulation by allogeneic lymphoid cells or by phytohemagglutinin. Such reactivity is much diminished in neonatal thymus or thymic-derived (T) cells in neonatal spleen. Splenic T cells seem to mature more slowly than immunoglobulin-bearing B lymphocytes in the neonatal spleen, but the finding is confounded by the presence of large numbers of "suppressor" T cells in the neonatal spleen. For example, the in vitro antibody response to the T-independent antigen dinitrophenyl-lysine-Ficoll is optimal by 2 or 3 weeks of age, but the in vitro response to T-dependent sheep erythrocytes does not reach adult levels until 6 weeks of age, suggesting a deficiency in T "helper cells." The response of neonatal spleen cells to sheep erythrocytes cannot be reconstituted by adult T cells however, unless neonatal splenic T cells are first depleted by anti-Thy 1 serum and complement. The target of this T suppressor cell seems to be only B cells, and not other T cells. The overall sequence of T lymphocyte maturation in the mouse seems to start with large numbers of reactive T cells as well as some functionally active helper or effector T cells in early neonatal life, and finally to achieve a stable equilibrium between T cell subpopulations between 5 and 6 weeks of age.

Animals↗
PubMed1975

Immunologic effects of neonatal infection with mouse thymic virus.

Mouse thymic virus is a herpesvirus that causes extensive thymic necrosis when given to newborn mice. During the time of acute infection spleen cells have markedly diminished reactivity to T cell phytomitogens and to allogeneic cells and are incapable of effecting a primary in vitro response to a "T-dependent" antigen; responses to B cell mitogens and to a T-independent antigen are unimpaired. Spleens from acutely infected mice have low theta antigen normal numbers of immunoglobulin-bearing cells. Surprisingly, despite widespread necrosis and cellular depletion, thymic cell reactivity to mitogens is unimpaired. However, the ability to thymocytes to proliferate and to generate cytotoxic killer cells in response to allogeneic cells is diminished.

Animals↗
PubMed1974

Cellular requirements for the primary in vitro antibody response to DNP-ficoll.

The cellular requirements for the primary in vitro IgM and IgG response to dinitrophenyl-substituted Ficoll were examined. Neither thymus-derived lymphocytes nor macrophage-rich splenic adherent cells were required for anti-DNP antibody synthesis. DNP-Ficoll is therefore tentatively classified as a "thymic-independent" antigen.

Animals↗
PubMed1972

Functional maturation of thymic lymphocyte populations in vitro.

Mouse thymocytes were cultured for short periods of time either alone or with one of two supporting cell populations, splenic adherent cells or thymic epithelial cells. The thymus-derived (T) cell activity of thymocytes cultured on supporting cell populations increased dramatically during 2 days of culture, as assayed in the mixed lymphocyte interaction (MLI), response to phytomitogens, and helper cell activity in the in vitro antibody response. The level of activity attained was equal to that of spleen and lymph node lymphocytes and greater than that of steroid-resistant thymocytes. The cultured thymocytes had surface antigens characteristic of mature T lymphocytes with regard to theta and H-2. The appearance of functionally active lymphocytes in vitro depended upon cell division. Most of the active cultured cells arose from cells already undergoing maturation, i.e., from cells with reduced theta determinants and increased H-2 determinants. We therefore have generated a population of thymocytes indistinguishable from peripheral T lymphocytes using simple in vitro techniques. The extent to which the production of these active lymphocytes depends upon in vitro differentiation is discussed.

Animals↗
PubMed1969

Cell interactions in the primary immune response in vitro: a requirement for specific cell clusters.

Mouse spleen cells were found to associate in cell clusters during the primary immune response to sheep erythrocytes in vitro. About 10% of the cell clusters had the following unique properties; (a) they contained most, if not all, antibody-forming cells, (b) they contained only cells forming antibody to one antigen when cell cultures were immunized with two antigens, (c) the cells in clusters reaggregated specifically after dispersion, and (d) the specific reaggregation of clusters appeared to be blocked by antibody to the antigen. The integrity of cell clusters was required for the proliferation of antibody-forming cells, and prevention of clustering by mechanical means or by excess antibody blocked the immune response. Antibody and antigenic determinants on the surfaces of cells probably provide the basis for interaction. The unique microenvironment of cell clusters was essential for the primary immune response in vitro.

Animals↗
PubMed1968

The rate of division of antibody-forming cells during the early primary immune response.

Mitotic blocking agents, colchicine or Velban, were used to estimate cycle times of spleen cells which release hemolysin for sheep erythrocytes (plaque-forming cells). The cells were obtained either from rats immunized with sheep erythrocytes or from cultures of mouse spleen cells immunized in vitro with the same antigen. 2, 3, or 4 days after immunization, animals or cell cultures were treated with mitotic blocking agents for periods of time ranging from 2.5 to 7 hr; plaque-forming cells were then enumerated. Decreased numbers of plaque-forming cells were found after such treatment. The extent of reduction was a function of duration of the drug treatment and the method of immunization, but was independent of the time after immunization. The evidence presented is consistent with premises that: (a) plaque-forming cells in mitosis do not release sufficient antibody to be detected, (b) mitotic blocking agents, by arresting plaque-forming cells in metaphase, prevent not only detection of these cells but also the increase in number of plaque-forming cells which would have resulted from cell division, (c) mitotic blocking agents do not affect release of antibody by cells in interphase. Cell cycle times, based on the extent of reduction of plaque-forming cells per unit time of drug treatment, were estimated using a mathematical model appropriate for an exponentially increasing population of cells. Cell cycle times estimated using the mitotic blocking agents agreed well with cell doubling times calculated from the increase in plaque-forming cells occurring 1-4 days after immunization. Increased responses produced by higher antigen doses or treatment of immunized animals with an adjuvant resulted from an increased rate of division of responding cells and their progeny. The results are consistent with a cell selection theory of antibody formation. Antigenic stimulation causes relatively few cells to proliferate and to synthesize antibody; apparently the magnitude of the response is dependent primarily on the rate of division of responding cells. It is suggested on the basis of observations of in vitro-immunized cell cultures that the rate of division of responding cells may be dependent on the rate of interaction between two cell types, both of which are essential for the in vitro plaque-forming cell response.

Animals↗