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Biomedical subjects

D E Mosier

Publications and source records attributed to D E Mosier.

At least 109 records · Page 6Linked to original sources
PubMed1979

Lyb-7, a new B cell alloantigen controlled by genes linked to the IgCH locus.

Anti-Lyb-5.1 serum contains antibodies against two different B cell surface antigenic determinants, Lyb-5.1 and Lyb-7.1, which are defined in cytotoxicity and functional tests, respectively. The antibody against Lyb-7.1 is identified by its ability to specifically inhibit in vitro primary antibody responses to TNP-Ficoll. Anti-Lyb-5.1 serum can be made monospecific for anti-Lyb-7.1 activity by absorption with spleen cells from AL/N mice which have been typed as Lyb-5.1+, Lyb-7.1-. Lyb-5.1 and Lyb-7.1 are each under control of one or one set of closely linked genes. The loci specifying Lyb-5.1 and Lby-7.1 are not linked to each other nor to M1s and H-2 loci. However, the gene controlling the expression of Lyb-7.1 is linked to the genes coding for the constant region of immunoglobulin heavy chains.

Animals↗
PubMed1978

Activation of mouse lymphocytes by anti-immunoglobulin. II. A thymus-independent response by a mature subset of B lymphocytes.

Mouse spleen cells can be stimulated to proliferate in vitro by purified anti-mu or anti-gamma,kappa antibodies. These responses can be obtained in cell populations bearing membrane immunoglobulin (Ig), purified by the fluorescence activated cell sorter (FACS), but they are not observed in FACS-purified Ig- cell populations. Furthermore, treatment of spleen cell populations with anti-Thy 1.2 and complement does not impair the response, nor does addition of nylon wool-purified T lymphocytes enhance it. These results indicate that B lymphocytes respond to anti-Ig and that their response does not require T cells. On the other hand, cells from athymic nude (nu/nu) mice respond slightly less well to anti-mu than do cells from heterozygous littermate (nu/+) controls; nu/nu cells are almost unresponsive to anti-gamm,kappa and addition of nylon wool-purified T cells from nu/+ controls does not restore the response. This suggests that T lymphocytes or the thymus may control the appearance of cells responsive to anti-gamma,kappa. Responsiveness of normal mice to anti-mu does not appear until 4 wk of age and does not reach maximum levels until 8 wk of age. Acquisition of full responsiveness to anti-gamma,kappa is even more delayed. This, together with the failure of mice with the CBA/N B-cell defect to respond to anti-Ig, suggests that cells stimulated to proliferate by anti-Ig are a mature subset of B cells. Depletion of adherent cells by Sephadex G-10 treatment or by treatment with carbonyl iron and exposure to a magnetic field does not diminish anti-mu or anti-gamma,kappa responses, suggesting that the responsiveness does not require the presence of macrophages. Thus, activation of B-cell proliferation by anti-Ig appears to be a T-cell independent, macrophage-independent process in which membrane Ig plays a direct role in signal generation.

Animals↗
PubMed1978

Anti-idiotype induced regulation of helper cell function for the response to phosphorylcholine in adult BALB/c mice.

An adoptive secondary antibody response to phosphorylcholine (PC) can be generated by the transfer of keyhole limpet hemocyanin (KLH)-primed T cells, PC-bovine gamma globulin-primed B cells, and PC-KLH into irradiated syngeneic BALB/c mice. If the KLH-primed T-cell donors were pretreated with anti-idiotype antibodies directed against the BALB/c PC-binding myeloma TEPC 15, their T cells were unable to collaborate effectively with PC-primed B cells; moreover, they could suppress the helper activity of T cells from normal mice for the PC-KLH response. The Ly phenotype of these T cells was found to be Ly 1-, 2+. The specificity of the suppressor T-cell population induced by anti-T15 treatment appears to be both for idiotype (hapten) and carrier, since the suppressor T cells fail to interfere with the antibody response to PC on a heterologous carrier, nor do they suppress the response to trinitrophenol-KLH.

Animals↗
PubMed1978

Activation of mouse lymphocytes by anti-immunoglobulin. I. Parameters of the proliferative response.

Spleen cell cultures from young adult mice of a variety of strains were stimulated to incorporate tritiated thymidine ([3H]TdR) by a goat anti-mouse IgM antiserum and by purified anti-mu antibodies prepared from this serum. This stimulation was shown to depend upon the anti-mu activity of the antiserum. In addition, ultracentrifuged anti-mu and F(ab')2 fragments of anti-mu were shown to be stimulatory. The anti-mu preparation lacked detectable endotoxin contamination and was also shown to stimulate response by two strains (C57BL/10ScCr and C3H/HeJ) which are unresponsive to the mitogenic effects of endotoxin, while it failed to stimulate a response by cells from a mouse strain (CBA/N) which responds to endotoxin. In addition purified goat anti-mouse gamma, kappa antibodies and rabbit anti-mouse kappa-antib odies stimulated uptake of [3H]TdR by mouse spleen cells, although to a lesser degree than the anti-mu preparation. The cell density, culture requirements, and kinetics of the response are presented.

Animals↗
PubMed1978

T-independent responses in B cell-defective CBA/N mice to Brucella abortus and to trinitrophenyl (TNP) conjugates of Brucella abortus.

CBA/N mice have an X-linked immune defect in B lymphocyte function which leads to their inability to respond to several thymus-independent antigens. We report here that these mice and immunologically defective F1 male (CBA/N X DBA/2N) mice can respond to Brucella abortus and to 2,4,6-trinitrophenyl derivatives of Brucella abortus (TNP-BA). These responses can be obtained in vivo and in vitro and are thymus-independent by the criteria that (a) they can be transferred to irradiated recipients by bone marrow cells and anti-Thy-1.2 and complement-treated spleen cells; (b) that nu/nu BALB/c spleen cells respond to TNP-BA in vitro; and (c) that anti-Thy-1.2 and complement-treated (CBA/N X DBA/2N)F1 male spleen cells respond to TNP-BA in vitro. B. abortus and TNP-BA are poor polyclonal B cell activators (PBA) and poor B cell mitogens, unlike lipopolysaccharide which is both a powerful PBA and B cell mitogen. These results therefore indicate that mice with the CBA/N B cell defect can respond to some thymus-independent antigens, namely TNP-BA, and as shown previously, TNP-LPS, although not to other thymus-independent antigens. This, in turn, suggests that thymus-independent antigens may be subdivided on the basis of their ability or inability to stimulate responses by CBA/N B lymphocytes.

Animals↗
PubMed1978

B lymphocyte development, heterogeneity, and function.

Thymus-independent (B) lymphocytes are a heterogeneous group of cells which, it is increasingly clear, undergo an ordered sequence of differentiation steps from stem cells to antibody producing cells. Through the study of the immunologic potential of B lymphocytes from neonatal mice and from mice with an X-linked immune defect, it has become possible to assign certain functions to cells of distinct differentiated states. Furthermore, a differentiation antigen, Lyb 5, has been identified which acts as a marker of a particular subset of B lymphocytes in normal mice. Initial studies of the functional properties of Lyb 5+ and Lyb 5- B lymphocytes are described.

Animals↗
PubMed1978

Induction of B cell priming by neonatal injection of mice with thymic-independent (type 2) antigens.

Mice injected at birth with the thymus-independent type 2 antigen TNP-AECM-Ficoll have augmented anti-TNP antibody responses when their spleen cells subsequently are challenged in vitro with TNP-coupled thymic independent or thymic dependent antigens. This neonatal priming effect was shown to occur in neonatal nu/nu mice and thus does not appear to require T lymphocytes. The primary explanation for the priming effect seems to be an increase of approximately 10-fold in the numbers of TNP-specific precursors of antibody-forming cells. The neonatal injection of TNP-AECM-Ficoll induces little or no antibody formation directly. It appears, therefore, that some thymic independent antigens can deliver a signal to immature B cells, which causes clonal expansion, but is unable to induce differentiation into antibody-forming cells.

Animals↗
PubMed1977

The role of surface IgD in the response to thymic-independent antigens.

An alloanti-delta antibody was prepared by immunizing C57BL/Ka mice with BALB/c spleen cells. Its specificity for delta-chain was demonstrated by immunoprecipitation and SDS-PAGE of 125I-labeled membrane proteins from BC8 spleen cells. BC8 mice possess C57BL/Ka "background" genes and BALB/c IgH genes. The anti-delta reagent without complement inhibited the primary in vitro anti-TNP antibody response to TNP-AECM-Ficoll by BC8 spleen cells, although it had no effect of the anti-TNP response of congenic C57BL/Ka spleen cells, which lack the delta-allotype identified by this antibody. On the other hand, the anti-delta antibody had no effect on the anti-TNP response of BC8 spleen cells to TNP-BA, except at limiting antigen concentrations. Both TNP-AECM-Ficoll and TNP-BA are T-I antigens, but they differ in that TNP-AECM-Ficoll fails to stimulate in vitro responses by immunologically defective CBA/N and neonatal spleen cells whereas TNP-BA can cause responses from both these animals. These results suggest that the IgD receptor is critical to T-I antibody responses initiated by TNP-AECM-Ficoll but that it is not required for T-I responses stimulated by TNP-BA.

Animals↗
PubMed1977

Ly phenotype and mechanism of action of mouse neonatal suppressor T cells.

Neonatal suppressor T cells were isolated from the thymuses of 10- to 14-day old BDF mice infected at birth with mouse thymic virus. Such cells were enriched for suppressive activity directed against antibody formation by adult B cells and represented a relatively homogenous population of outer cortical cells. Their surface antigen phenotype was found to be: Ly 1+, Ly 2+, TL+, Thy 1+, and H-2+. The cells were larger and contained more DNA than thymocytes from age-matched controls. These findings identify neonatal suppressor T cells as a unique subpopulation separate from most inducible suppressor cells in the adult mouse. The mechanism of action of neonatal suppressor T cells seems to be a reduction in the number of B cells initially triggered by antigen.

Animals↗
PubMed1977

Formation of antibody in the newborn mouse: study of T-cell-independent antibody response.

The ontogeny of immune responsiveness, as assayed by antibody formation in vitro, of mouse spleen lymphocytes to thymus-independent antigens is reviewed. Responsiveness to trinitrophenyl (TNP)-lipopolysaccharide and TNP-Brucella abortus appear soon after birth and one to two weeks before TNP-Ficoll or capsular polysaccharide of Streptococcus pneumoniae (SSS-III) elicits significant antibody formation. This hierarchy of responsiveness to antigens is also apparent in the CBA/N mutant mouse strain, which has a bone marrow-derived (B-) cell maturation arrest and fails to respond to either TNP-ficoll or SSS-III. These findings are interpreted to suggest sequential maturation of different populations or lines of B-lymphocytes, each of which can respond to a defined class of thymus-independent antigens. The implication for vaccine use in humans is that a late-appearing subclass of B-cells may be required for adequate immune responses to polyaccharide antigens.

Age Factors↗
PubMed1977

The ontogeny of thymic independent antibody responses in vitro in normal mice and mice with an X-linked B cell defect.

The primary in vitro antibody response of neonatal spleen cells to three thymic independent antigens has been examined. The time of onset of responsiveness to TNP-Brucella abortus and TNP-lipopolysaccharide was significantly earlier than the onset of responsiveness to TNP-Ficoll. This ontologic sequence was not affected by T cell depletion or antigen presentation on adult macrophages. In neonatal mice bearing the X-linked CBA/N defect, the response to TNP-Brucella abortus and TNP-lipopolysaccharide was much delayed and no response to TNP-Ficoll developed. We conclude that different thymic independent antigens address different subpopulations of B cells, one of which appears earlier in ontogeny than the other.

Animals↗
PubMed1976

Specific loss of stimulator activity following mixed lymphocyte reactions is due to cytotoxic cells.

Experiments were performed to test the hypothesis that stimulating antigens in the mixed lymphocyte reaction (MLR) are expressed in a restricted fashion on lymphocytes. Thus one-way MLR between spleen cells from congenic mouse strains differing at H-2 were treated with 5-bromo-2-deoxyuridine (BrdUrd) and light to inactivate dividing cells. The ability of the residual cells to act as responder or stimulator cells in a subsequent MLR was assessed. As expected, a specific loss of responder cell activity occurred under these conditions. Furthermore, such cells, following irradiation, would not stimulate fresh spleen cells from the strain against which they initially responded, but would stimulate spleen cells, following irradiation, would not stimulate fresh spleen cells from the strain against which they initially responded, but would stimulate spleen cells of unrelated mouse strains. This was shown to be due to the generation of cytotoxic T cells detectable in 51Cr release assays in the primary MLR, despite BrdUrd and light treatment and irradiation. Furthermore, loss of stimulator activity mapped to the H-2K region of the H-2 complex rather than the strong MLR-stimulating I-A or I-B subregions. These experiments provide no evidence of restricted expression of MLR-stimulating antigens on lymphocytes.

Animals↗
PubMed1976

In vitro studies of the genetically determined unresponsiveness to thymus-independent antigens in CBA/N mice.

The X-chromosome-linked B lymphocyte defect of CBA/N mice has been studied in vitro by comparing the ability of (CBA/N X DBA/2)F1 (X-/X- X X+/Y) male (X-/Y) and female (X-/X+) spleen cells to respond to the thymus-independent antigen DNP (or TNP)-AECM-Ficoll. (CBA/N X DBA/2)F1 male spleen cells failed to generate significant in vitro anti-TNP antibody responses to DNP- or TNP-AECM-Ficoll, in contrast to spleen cells from F1 female (X-/X+) mice which responded normally to these T-independent antigens. Spleen cells from male F1 mice responded almost as well as F1 female cells to the thymus-dependent antigen, TNP-sheep red blood cells (TNP-SRBC) in vitro. Adding F1 male cells to F1 female cells failed to reduce the response of the latter to DNP-AECM-Ficoll, suggesting that the inability of F1 male cells to respond was not due to active suppression. The response of F1 male spleen cells to TNP-SRBC was not impaired by adding high concentrations of TNP-AECM-Ficoll indicating that the mechanism of unresponsiveness was not tolerance induction in all TNP-specific precursors. Lymphocytes from F1 male mice were capable of forming anti-TNP antibody after stimulation with lipopolysaccharide (LPS) in high concentrations; DNP-AECM-Ficoll had no effect on this polyclonal response. B lymphocytes from mice bearing only the X-chromosome of the CBA/N strain thus display a profound defect in B cell activation. This functional defect may represent either an inability of the defective B cells to be activated by thymus-independent antigens or the absence of a sub-class of B cells which respond to thymus-independent antigens.

Animals↗
PubMed1976

Macrophage requirement for the in vitro response to TNP Ficoll: a thymic independent antigen.

The in vitro antibody-forming cell response of mouse spleen cells to the thymic independent synthetic polymer, TNP-Ficoll, was found to require the presence of either macrophages or 2-mercaptoethanol. The TNP-Ficoll response and that to the thymic dependent antigen, sheep erythrocytes, demonstrated the same degree of macrophage dependence. However, macrophage-depleted spleen cells which did not produce plaque-forming cells responded normally to T and B cell mitogens. Comparison of the antibody-forming cell response of macrophage-depleted spleen cells in the presence and absence of 2-mercaptoethanol indicated that either macrophages function 10 to 100 times more efficiently in its presence or that 2-mercaptoethanol partially replaces the function of macrophages.

Animals↗