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Biomedical subjects

W E Paul

Publications and source records attributed to W E Paul.

At least 19 recordsLinked to original sources
PubMed1979

Cellular basis of regulation of expression of idiotype. II. Immunity to anti-MOPC-460 idiotype antibodies increases the level of anti-trinitrophenyl antibodies bearing 460 idiotypes.

The antibody response of BALB/c mice to trinitrophenyl (TNP)-levan or TNP-Nocardia water-soluble mitogen (NWSM) includes a small but significant fraction of antibodies which share idiotypes (Id) with the dinitrophenyl (DNP)- and TNP-binding myeloma protein MOPC-460. Active immunization of BALB/c mice with MOPC-460 or passive administration of anti-460-Id antibodies suppresses the 460-Id+ component of the anti-TNP response. By contrast, active immunization of BALB/c with anti-460-Id antibodies or passive administration of BALB/c anti-[anti-460-Id] antibodies leads to an enhanced 460-Id+ component in the anti-TNP antibodies produced in response to TNP-levan or TNP-NWSM. This enhanced 460-Id+ response appears to be a result of the elimination of suppressor T lymphocytes specific for the 460-Id as T lymphocytes from such mice are unable to suppress the in vitro 460-Id+ response to TNP-NWSM whereas normal T cells are suppressive. These results indicate that suppressor cells specific for 460-Id normally regulate the activation of precursors of cells capable of secreting 460-Id+ anti-TNP antibodies.

Animals↗
PubMed1979

Immunoglobulin subclass-specific immunodeficiency in mice with an X-linked B-lymphocyte defect.

CBA/N mice express an X-linked deficiency in their antibody response to many bacterial carbohydrates; we have shown recently that these antigens normally elicit antibody responses predominantly of the IgM and IgG3 isotypes. Here we demonstrate that mice, with the CBA/N phenotype have perferential deficiencies of IgM and IgG3 immunoglobulin expression, both when measured in serum and in cells secreting these isotypes, and that this deficiency is only partially corrected by polyclonal activation of B cells. This suggests that CBA/N mice may lack a subpopulation of B cells that contain most of the IgG3 precursors.

Animals↗
PubMed1979

Cellular basis of regulation of expression of idiotype. I. T-suppressor cells specific for MOPC 460 idiotype regulate the expression of cells secreting anti-TNP antibodies bearing 460 idiotype.

An idiotype of the dinitrophenyl-binding myeloma protein MOPC 460 was expressed on a small but significant proportion of anti-TNP antibodies which appeared after in vivo or in vitro immunization of BALB/c mice with three T-independent TNP antigens. In vitro experiments show that the depletion of T cells before culture increased significantly the number of plaques secreting anti-TNP antibodies bearing MOPC 460 idiotype (460Id). T cells from BALB/c mice, but not from C.B20 mice, exhibit this suppressor activity. Plate-binding experiments indicate that the suppressive action of the T-lymphocyte population depends on a cell which can bind to MOPC 460 myeloma protein. The possible role of these normally occurring, idiotype-specific T cells on expression of 460Id in the anti-TNP antibody response of BALB/c mice is discussed.

Animals↗
PubMed1979

Role of a nonimmunoglobulin cell surface determinant in the activation of B lymphocytes by thymus-independent antigens.

Lyb 5 is a B-cell alloantigen which is expressed on 50-60% of B cells. It was defined originally on the basis of cytotoxicity. We have described a new reactivity within the anti-Lyb 5 serum on the basis of selective inhibition of antibody responses in vitro by this antiserum in the absence of complement. This inhibitory activity of anti-Lyb 5.1 serum appears to be due to recognition of antigenic determinants different from the prototype antigens detected in the cytotoxicity assay. Anti-Lyb 5 serum incorporated into spleen cell cultures selectively inhibits antibody responses to a class of thymus-independent antigens (TI-2) previously characterized by their failure to elicit antibody formation in immature mice or in the defective CBA/N strain. Responses to optimal concentrations of TI-1 antigens, which can induce antibody synthesis in these mice, are unaffected by the addition of anti-Lyb 5.1 serum. The B-cell alloantigen defined by this functional assay is designated tentatively Lyb 7 and it is shown to be distinct from cell surface immunoglobulins. Lyb 7 appears to have a role in the activation of B lymphocytes by the TI-2 class of thymus-independent antigens.

Antibody Formation↗
PubMed1979

Gene complementation in the T-lymphocyte proliferative response to poly (Glu55Lys36Phe9)n. A demonstration that both immune response gene products must be expressed in the same antigen-presenting cell.

The immune response (Ir) to the random copolymer GLphi depends upon the function of two Ir genes, Ir-GLphi-beta[beta] and Ir-GLphi-alpha[alpha], mapped to the I-A and I-E/C subregions of the major histocompatibility complex, respectively. In this paper, the site(s) of expression of the products of these two Ir genes was examined by evaluating T-lymphocyte proliferative responses of bone marrow radiation chimeras. Chimeras were created in [alpha+beta- X alpha-beta+]F1 responder mice by lethal irradiation and reconstitution with a mixture of bone marrow cells from both parental strains. These chimeras failed to respond to GLphi, although they were capable or responding to the much weaker antigens, (T,G)-A--L, TEPC-15, pigeon cytochrome c, and (H,G)-A--L. This failure to respond to GLphi was shown not to be the result of a cryptic mixed lymphocyte reaction, as similar chimeras created in (alpha+beta+ X alpha-beta+)F1 mice responded well to GLphi, although they possessed almost the same potential histoincompatibility. Furthermore, the lack of response to GLphi could not be attributed to a general failure of the two parental cell types in the chimeras to collaboratc with each other, as each chimeric parental cell type could respond to dinitrophenyl conjugated ovalbumin presented on nonimmune spleen cells from the other parent. Thus, the failure of low responder parental into F1 high responder chimeras to generate an immune response to GLphi suggests that immune competence for this antigen requires at least one cell type in the immune system to express gene products of both the Ir-glphi-alpha and -beta genes, i.e. one cell must be of high responder genotype. The the antigen-presenting cell is one such cell type was shown by experiments in which GLphi-primed T lymphocytes from responder F1 mice were stimulated with antigen bound to nonimmune spleen cells. Only spleen cells from responder F1 and recombinant mice could present GLphi. Neither of the two complementing nonresponder parental spleen cell populations, either alone or mixed together, could present GLphi, although both could present purified protein derivative of tuberculin. This was shown to be the case for T cells positively selected in vitro as well as freshly explanted T cells. Thus, both Ir-GLphi-alpha and Ir-GLphi-beta gene products must be expressed in the same antigen-presenting cell to generate a T-lymphocyte proliferative response to GLphi. The implications of these findings for models of two gene complementation are discussed.

Animals↗
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↗
PubMed1979

Immune response to levan. II. T independence of suppression of cross-reactive idiotypes by anti-idiotype antibodies.

Pretreatment of BALB/c mice with antisera to a cross-reactive idiotype (E109IdX) expressed on many anti-bacterial levan (BL) and anti-inulin (Inu) antibodies leads to a prolonged suppression in production of IdX-bearing molecules in response to BL immunization. There is a comparable suppression in numbers of plaque-forming cells secreting IdX-bearing anti-BL and anti-Inu molecules. Furthermore, spleen cells from anti-E109IdX pretreated mice are unable to transfer to irradiated recipients the ability to produce IdX-bearing anti-BL and anti-Inu antibodies. These results indicate that the suppressive effect is at the precursor level and not simply a clearance of antibodies bearing the IdX. Suppression of IdX production can be achieved by pretreating nu/nu BALB/c mice with anti-E109IdX antibodies. Furthermore, spleen cells from pretreated mice do not inhibit the capacity of spleen cells from normal mice transferred to irradiated recipients to produce E109IdX in response to BL. This indicates that the suppression of IdX production in the anti-BL system is T independent and probably represents direct inhibition of precursors by anti-IdX.

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

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

Antigen presentation in the murine T lymphocyte proliferative response. II. Ir-GAT-controlled T lymphocyte responses require antigen-presenting cells from a high responder donor.

The activation of T lymphocytes from poly (Glu60Ala30Tyr10)n (GAT)-primed donors by GAT-pulsed nonimmune spleen cells was shown to require identity at the I-1 subregion of the major histocompatibility complex. However, GAT-primed T lymphocytes from (responder x nonresponder) F1 hybrids could only be stimulated to proliferate by GAT bound to high responder or F1 spleen cells but not by GAT bound to spleen cells from the low responder parent. The failure of spleen cells from low responder parental strains to present GAT was shown not to be due to the presence of suppressor cells in either the antigen-presenting or the responding cell populations. These results indicate that control of antigen-presenting cell-T lymphocyte interactions is one site of Ir gene expression.

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

Inhibition of dual Ir gene-controlled T-lymphocyte proliferative response to poly (Glu56Lys35Phe9)n with anti-Ia antisera directed against products of either I-A or I-C subregion.

Previous studies have demonstrated that both the antibody and T-lymphocyte proliferative immune responses to poly(Glu53Lys36Phe11)n (GLphi) are under the control of two major histocompatibility-linked immune response (Ir) genes. One gene, termed Ir-GL phi-alpha, has been mapped to the I-C or I-E subregion of the major histocompatibility complex, while the other, termed Ir-GL phi-beta, has been mapped to the I-A subregion. In this paper we examine the effect of anti-I-region-associated (Ia) antisera on the T-lyphocyte proliferative response to GL phi. Antibodies directed against Ia antigens coded for by genes in either the I-A or I-C subregion were found to inhibit the proliferative response to GLphi. These results suggest that a function mediated by two Ir gene products can be blocked by anit-Ia antisera directed against either one, and thus, that both products are expressed on the cell surface.

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↗