bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ir Gene Regulation at the Single Cell Level
Authors: Pierce S. K. , Klinman N. R. 
Published: December 2022

Abstract
Extensive genetic, cellular and molecular studies have suggested that I region cell surface gene products of the MHC play an important role in cell-cell recognition during T-dependent humoral immune responses. Our own studies have demonstrated that sharing of genes in the Ir-1A or Ir-1B subregions of the I region (as defined by the B10.A(5R) and B10.A(4R) combination) between collaborating T and B lymphocytes is essential for primary B-cell stimulation to IgG1 antibody synthesis in response to DNP-Hy. We have utilized the I region genetically controlled responses to the polymer GLϕ to better define the precise nature of recognition restrictions in T cell-B cell interactions in antibody responses to DNP-GLϕ in the splenic fragment culture system. In this system syngeneic and allogeneic T cell-B cell collaborations can be discriminated by virtue of the Ig heavy chain isotope of the antibody which is synthesized as a result of the cell-cell interaction.
Conjugate Formation by Primary and Secondary Populations of Murine Immune T Lymphocytes
Authors: Glasebrook Andrew L. 
Published: December 2022

Abstract
Primary (1°) and secondary (2°) murine immune T lymphocyte populations generated in vivo and in vitro exhibit differences in the rate of target cell-specific conjugate formation. Populations containing secondary CTL reached maximum conjugate formation after 10 to 15 min when mixed with target cells (1:1) and centrifuged at 4°C followed by incubation at 37°C, whereas primary alloimmune T lymphocytes required 20 to 30 min of incubation. Cytolytic activity was measured concurently during the incubation period by a 51Cr release-EDTA assay. Although populations of 1° and 2° immune T lymphocytes reached similar levels of maximum conjugate formation during incubation, cytolytic activity at the time of maximum conjugate formation was insignificant compared to that obtained after 3.5 hr of incubation. Also, long-term 1° MLC cells that exhibit very little cytolytic activity formed specific conjugates, as did all effector cell populations in the presence of EGTA, a Ca++ chelating agent that inhibited cytotoxicity 100%. This suggests that the expression of T lymphocyte alloantigen-specific membrane receptors and the binding of immune T cells to target cells are necessary but not sufficient for cytolysis. Repetitive killing of target cells by 2° CTL was suggested by the cytolytic activity after 3.5 hr when compared with the observed levels of maximum conjugate formation. Variations in the number, distribution, or affinity of alloantigen-specific receptors between 1° and 2° immune T lymphocyte populations may account for the observed differences in rates of conjugate formation.
Radiosensitivity of the Helper Cell Function
Authors: Agarossi Giovanna , Pozzi Laura , Mancini Camillo , Doria Gino 
Published: December 2022

Abstract
The helper function of T cells primed and irradiated in vivo was tested in vitro by the Mishell-Dutton technique. Spleen cells from mice carrier-primed with HRBC and exposed to 50 to 2000 rads of x-radiation were assayed for their ability to help syngeneic normal spleen cells to mount an in vitro anti-hapten antibody response after stimulation with the conjugate TNP-HRBC. The anti-TNP response was evaluated by the Jerne technique. The helper activity was titrated by adding graded numbers of carrier-primed spleen cells to a constant number of normal spleen cells. The slope of the initial linear portion of the response-cell dose titration curve was taken as an estimate of the helper activity and found to decrease with increasing the x-ray dose. The curve describing the remaining helper activity as a function of the radiation dose shows the presence of two components, one radiosensitive, the other, radioresistant. This suggests the existence either of helper cells at different stages of activation or of two cell subpopulations participating in the helper function.
Antigen-Induced Murine B Cell Lymphomas
Authors: Lynes Michael A. , Lanier Lewis L. , Babcock George F. , Wettstein Peter J. , Haughton Geoffrey 
Published: December 2022

Abstract
Two unusual murine lymphomas, designated CH1 and CH2, were produced in the newly developed double congenic strain of mice, B10 H-2a H-4bp/Wts. Both tumors lack the T cell-specific antigen (thy-1), but express cell surface immunoglobulin and the H-2K, H-2D, and Ia specificities determined by the H-2a haplotype. Further studies have demonstrated that these tumors represent “early” B cells in that they express surface IgM (µ heavy and λ light chains), but do not bear surface δ, γ, or α heavy chains. CH1 and CH2 lack surface C3 receptors and results from assays for Fc receptors have proven variable. A competition radioimmunoassay directed against the gp71 group-specific antigen of Friend leukemia virus has shown that there is a murine leukemia virus associated with these tumors, however, we have been unable to establish a causal relationship between the virus and this malignancy. A comparison of the surface characteristics of these tumors with other mammalian B cell lymphomas is presented.
Expression of Immunoglobulin Variable Region Antigens on Mouse B Lymphocytes
Authors: Stanislawski M. , Mitard M. 
Published: December 2022

Abstract
Rabbit antibodies prepared against two purified 7S BALB/c myeloma proteins, A2 (γ1, κ) and MOPC 195 (γ2b, κ), and solid-phase absorbed so as to contain only anti-heavy (H) chain specificities bound to 32 to 35% of C57BL/6 lymph node lymphocytes (about 80% of the B lymphocytes). A similar staining frequency was obtained with solid-phase absorbed antibodies to the Fab fragment and the heavy chain of the A2 protein. On the other hand, antibodies to other 7S proteins (MOPC 21 (γ1, κ), J606 (γ3, κ), and MOPC 173 (γ2a,κ)), as well as anti-Fc γ1, anti-Fc γ2a and anti-idiotypic antibodies either failed to bind to the cells, or bound to a small percentage of these. Employing a method of quantitative inhibition of cell-surface-binding capacity, it was found that the surface binding of the anti-A2 and anti-MOPC 195 antibodies was strongly inhibited by the MOPC 104E (µ, λ1) and J558 (α, λ1) proteins. There was also a reciprocal inhibition by the A2 and MOPC 195 proteins. Purified normal serum IgG1 and IgG2a were also strongly inhibitory. However, eight other BALB/c myeloma proteins of various classes were weakly, or noninhibitory. Only the homologous A2 Fab fragment, and H and light (L) chains inhibited the anti-A2 antibodies. The homologous and heterologous Fc fragments were not inhibitory. These results, added to the selective inhibitory behavior of the myeloma proteins, which is unrelated to either their H or L chain isotypic designation, suggest that the antigens involved are localized in H chain the variable region. The findings implicate that the bulk of C57BL/6 lymph node B lymphocytes expresses a surface H chain variable region subgroup antigen that corss-reacts with the A2, MOPC 195, MOPC 104E, and J558 myeloma proteins.
B Cell Heterogeneity
Authors: Quintáns J. , McKearn J. P. , Kaplan D. 
Published: December 2022

Abstract
Male (CBA/N × BALB/c) F1 hybrid mice cannot mount humoral immune responses to thymus-dependent (T.D.) or thymus-independent (T.I.) phosphorylcholine (PC) antigens and to trinitrophenyl (TNP)-AECM-Ficoll and TNP-AECM-dextran. Transplantation of spleen, bone marrow, or neonatal liver cells from BALB/c mice can restore responsiveness to these antigens. Engraftment of spleen and bone marrow cells occurs in unirradiated NBF1 hosts, whereas restoration of PFC responses by neonatal liver cells requires a sublethally irradiated NBF1 recipient. Reconstitution experiments demonstrated that the spleen contains T.D. and T.I. B cell precursors that can respond immediately to antigenic challenge, although the bone marrow contains only mature T.D. B cells and immature cells (progenitor cells) which will restore T.I. responses 2 weeks after transplantation. Neonatal liver cells contain only immature progenitor cells which, after 1 to 2 weeks in the NBF1 recipient, become antigen-reactive cells. In contrast to anti-TNP PFC responses, which are fully restored in all NBF1 recipients of BALB/c neonatal cells, only a fraction of NBF1 mice gain responsiveness to PC antigens. The frequency of successful reconstitutions of T.D. anti-PC PFC responses was higher than T.I. anti-PC responses. Idiotypic analysis in the reconstituted recipients demonstrated that H8 and non-H8 anti-PC PFC were being generated. Evidence is presented to indicate that the reconstitution with neonatal liver cells functionally resembles a limiting dilution assay for immature PC-specific progenitor cells, which include both H8 and non-H8 idiotype specificities in T.D. and T.I. anti-PC responses.
Human Immune Responses to Hapten-Conjugated Cells
Authors: Seldin Michael F. , Rich Robert R. , Dupont Bo 
Published: December 2022

Abstract
Proliferative responses of human lymphocytes primed in vitro to autologous TNP-cells were found to be associated with autologous D-region determinants irrespective of HLA-B locus antigens. Family studies of secondary TNP-conjugate proliferative responses demonstrated a gene dosage effect in this phenomenon. Moreover, co-culture with allogeneic cells did not affect the net TNP-conjugate proliferative responses of primed responder cells, suggesting that HLA-D region preference was due to a requirement for representation of TNP-molecules in association or combination with autologous MHC structures.
Alloantigens were found to influence the sensitization of lymphocytes to autologous hapten-conjugated cells. Co-culture of allogeneic and TNP-modified autologous stimulator cells in primary cultures enhanced the secondary TNP proliferative response. Sensitization of human lymphocytes to allogeneic cells alone did not prime responses to autologous modified cells. However, priming lymphocytes to modified autologous cells potentiated responses to allogeneic cells. The data suggest a complex relationship between responses to alloantigens and modified autologous cells.
Characterization of Lymphocyte-Activating Factor (LAF) Produced by Human Mononuclear Cells: Biochemical Relationship of High and Low Molecular Weight Forms of LAF
Authors: Togawa Atsushi , Oppenheim Joost J. , Mizel Steven B. 
Published: December 2022

Abstract
Human mononuclear cells (MNL) stimulated with Salmonella typhosa endotoxin (LPS), Actinomyces viscosus cell wall extracts, phorbol myristic acetate (PMA), or phytohemagglutinin (PHA) produced a factor that was mitogenic for mouse thymocytes. These agents not only enhanced the production of this mitogenic factor(s) by cultures of MNL enriched for glass-adherent cells, but also by nonadherent cell cultures. However, when the monocyte contamination of the nonadherent cell population was decreased to less than 0.5%, the remaining nonadherent cells did not generate significant thymocyte mitogenic activity, suggesting that either the contaminating monocytes were the cell source of the factor in the nonadherent cell population or that the production of the factor by nonadherent cells was monocyte dependent. The results of biochemical studies support the former possibility as follows: 1). The mitogenic activity produced by both adherent and nonadherent MNL eluted from Bio-Gel P-100 columns with m.w. of 50,000 to 70,000 and 12,000 to 22,000, values that are characteristic of the two forms of lymphocyte activity factor (LAF) produced by human monocytes. 2). The lower m.w. form of “thymocyte mitogenic” activity produced by the adherent as well as nonadherent MNL when characterized further both exhibited the same behavior on Bio-Gel P-100, DEAE cellular and hydroxylapatite. 3). When the lower m.w. LAF was reconstituted with 2% human serum, concentrated and rechromatographed on Bio-Gel P-100, a significant portion of the LAF activity appeared in the 50,000 to 70,000 m.w. range, suggesting that the higher m.w. form of LAF may actually be a complex of the lower m.w. LAF with a human serum component(s).
In conclusion, a small population of contaminating monocytes in a nonadherent MNL population is capable of producing significant amounts of LAF, and LAF may exist free or in association with a component(s) of human serum.
Limiting Dilution Analysis of Alloantigen-Reactive T Lymphocytes
Authors: Ryser Jean-Etienne , MacDonald H. Robson 
Published: December 2022

Abstract
The effect of specific priming with alloantigens on the frequency of cytolytic T lymphocyte precursors (CTL-P) has been investigated. Alloimmune lymphoid cells were obtained from the spleen of C57BL/6 (H-2b) mice primed with DBA/2 (H-2d) tumor cells or from 14-day unidirectional mixed leukocyte cultures (C57BL/6 anti-DBA/2). CTL-P frequencies directed against H-2d alloantigens were estimated by limiting dilution analysis in a sensitive micro MLC system. Under these conditions, an apparent increase of 3 to 4-fold in CTL-P frequency was observed in alloimmune (as compared with normal) C57BL/6 spleen cells. Evidence was obtained suggesting that this increase was specific for the priming alloantigens. A much greater increase in CTL-P frequency (25 to 100-fold) was observed after alloimmunization of C57BL/6 spleen cells in unidirectional MLC. Under the latter conditions, 5 to 20% of the surviving splenic MLC cells could be identified operationally as CTL-P. A similar enrichment in CTL-P frequency was obtained when lymph node, peripheral blood, or thymus cells were cultured 14 days in MLC. These studies provide direct evidence that the pool of specific CTL-P can be expanded after alloimmunization. Furthermore, the very high frequencies observed after in vitro priming indicate that this system should be particularly useful for future studies of the progeny of individual CTL-P.
Evidence that Natural Cytotoxicity and Antibody-Dependent Cellular Cytotoxicity Are Mediated in Humans by the Same Effector Cell Populations
Authors: de Landazuri Manuel O. , Silva Augusto , Alvarez José , Herberman Ronald B. 
Published: December 2022

Abstract
The present study strongly suggests that, in humans, natural killer (NK) activity and antibody-dependent cell-mediated cytotoxicity (ADCC) are mediated by the same effector cell population. This is supported by two different experimental approaches. First, competition for NK effector cells was accompanied by simultaneous inhibition of ADCC activity. Target cells sensitive to NK activity were capable of inhibiting specifically an ADCC assay in cold target competition experiments. Second, specific removal of NK cells on monolayers formed by target cells sensitive to NK activity caused simultaneous depletion of ADCC effector cells. In association with the removal on the monolayers of effector cells for ADCC as well as NK activity, we also found a significant depletion of cells bearing Fcγ receptors.
Virus-Induced Interferon Production by Human Macrophages
Authors: Roberts Norbert J. , Douglas R. Gordon , Simons Ruth M. , Diamond Margaret E. 
Published: December 2022

Abstract
The presence of interferon during viral infection in humans has been associated with the onset of the recovery process. The identity of the cell responsible for production of interferon in response to live virus has not been determined. Human peripheral blood mononuclear leukocytes, highly purified macrophages, and highly purified lymphocytes were exposed in vitro to influenza A virus. Interferon activity was detectable in the supernatant culture fluids of virus-exposed mononuclear leukocytes by 24 hr, was maximum by 72 to 96 hr, and declined thereafter. In each of eight experiments, supernatant fluid of virus-exposed macrophages contained interferon (100 to 800 units/ml, median 200 units/ml), but in none of the experiments was interferon detected in the supernatant fluid of control macrophages or virus-exposed or control lymphocytes. The interferon had characteristics of classical, Type I, interferon, and its activity was neutralized by rabbit antihuman leukocyte interferon globulin. Appearance of interferon activity in the supernatant fluid could not be attributed to cell death with release of preformed material. Adding lymphocytes to macrophages resulted in no increase in interferon activity in supernatant fluids in response to virus exposure, compared to macrophages alone. The results suggest a mechanism by which human macrophages may play an important role in human defense.
Macrophage-Mediated Tumor Cell Killing: Lack of Dependence on the Cyclooxygenase Pathway of Prostaglandin Synthesis
Authors: Shaw James O. , Russell Stephen W. , Printz Morton P. , Skidgel Randal A. 
Published: December 2022

Abstract
Mφ obtained directly from disaggregated murine Moloney sarcomas produced PGE2 and a hydroxy fatty acid derivative as the major products of arachidonic acid metabolism. Mφ-immunoreactive PGE synthetic rates decreased substantially and cytotoxic activity was lost when freshly explanted tumor Mφ were held in culture 24 hr. Such cultured Mφ remained in a partially activated “primed” state, however, wherein the addition of minute (ng) amounts of bacterial lipopolysaccharide (LPS) returned cytolytic activity and PGE synthesis to original levels. Indomethacin-induced blockade of the Mφ cyclooxygenase pathway inhibited PG synthesis by LPS-stimulated, primed Mφ without affecting the return of cytolytic activity. We conclude, therefore, that the production of PG had no direct role in the mediation of tumor cell killing by activated Mφ isolated from these neoplasms.
Characterization of Functional Fc-Receptor Material from Human Lymphoblastoid Cell Lines
Authors: Elliott Bruce E. , Takács Bèla J. 
Published: December 2022

Abstract
A xenogeneic anti-human Fc-receptor serum was prepared by injecting rabbits with Fc-receptor (FcR) material isolated from the NP-40 lysate of an IgM-secreting human lymphoblastoid cell line. By indirect immunofluorescence, the immune IgG (or F(ab′)2 fragment) from such animals reacted with a fraction of normal human peripheral blood leukocytes (PBL), corresponding closely to the proportion of FcR-bearing cells (assessed by immune complex binding), in the same cell population. The anti-FcR serum stained almost all the cells from five surface Ig-bearing lymphoblastoid cell lines, including the original cell line from which the FcR material was obtained, but not the FcR- T cell-like lymphoma, MOLT-4, phagocytic cells, or a granulocyte-like human cell line, K562. When human PBL were incubated with anti-FcR serum, the proportion of rosettes subsequently formed with antibody-sensitized ox erythrocytes (EA) was greatly reduced. The inhibitory activity of the antiserum was removed when it was absorbed with human PBL enriched for EA rosette-forming cells (RFC), but not human PBL depleted of such cells (T cells). The antiserum reacted with a fraction of Ig-bearing lymphocytes in normal mouse spleen and PBL, and with allogeneic activated T cells (30 to 40% FcR+) from irradiated F1 hybrid mice transplanted with parental T cells, but not with normal thymocytes. The determinants recognized by the anti-FcR serum are distinct from serologically detectable β2 microglobulin, HLA, H-2 and Ia-like determinants: a) The anti-FcR serum precipitated from an NP-40 lysate of a human lymphoblastoid cell line (WT-18), material with an apparent m.w. of 46,000 daltons and that appears distinct from Ia molecules or β2 microglobulin. b) The anti-FcR serum did not react with MOLT-4 cells nor with T cells in normal human PBL, mouse spleen, and thymus, although these cells express serologically detectable HLA or H-2 specificities. c) The anti-FcR serum, but not an anti-human Ia-like serum, reacted with normal mouse spleen cells. d) The anti-FcR serum reacted with an FcR+ T cell tumor, but not with an FcR- T cell tumor, both derived from the same AKR lymphoma.
Activation of Human B Lymphocytes
Authors: Dimitriu Alexandra , Haynes Barton F. , Fauci Anthony S. 
Published: December 2022

Abstract
The precursor of the pokeweed mitogen (PWM)-induced anti-sheep red blood cell (SRBC) plaque-forming cell (PFC) in human peripheral blood was characterized. By a variety of purification procedures, it was demonstrated to be a lymphocyte with surface characteristics of a B cell. Furthermore, it was demonstrated to bind to sheep erythrocytes (E) and thus segregated with the E-rosetting T cells when T cell enrichment was performed by differential fractionation of E-rosetting cells. This binding of the PFC precursor to E was blocked by pretreating the lymphocyte with anti-human Ig before E rosetting, indicating that the PFC precursor specifically bound to SRBC by a surface Ig molecule with binding specificity for sheep red blood cell determinants. Hence, the precursor of the PWM-triggered anti-SRBC PFC is a B lymphocyte with surface Ig expressing specificity for SRBC.
Suppression of Adult B Cell Differentiation in Pokeweed Mitogen-Stimulated Cultures by Fc(IgG) Receptor-Negative T Cells from Cord Blood
Authors: Moriya Naoki , Nagaoki Takeshi , Okuda Norihiko , Taniguchi Noboru 
Published: December 2022

Abstract
Unfractionated T lymphocytes from cord blood suppressed adult B cell differentiation into immunoglobulin-producing cells in pokeweed mitogen-stimulated co-culture system. Cord blood T cells were fractionated into T cells bearing Fc receptors for IgG(Tγ cells) and T cells lacking Fc receptors for IgG(Tnon-γ cells) by rosette formation with ox erythrocytes coated by the IgG fraction of rabbit antisera followed by Ficoll-Hypaque gradient sedimentation. Tγ cells from cord blood, even though isolated after the interaction with immune complexes, showed no suppressor activity on adult B cell differentiation, whereas Tnon-γ cells exerted strong suppression to a similar extent to that by unfractionated cord T cells. The suppressor activity on B cell differentiation by Tnon-γ cells as well as by unfractionated T cells from cord blood was completely abrogated by irradiation with 2000 rads. These results indicated that, contrary to suppressor function found in adult T cells, the suppressor activity in cord T cells might be exerted by a T cell subset lacking Fc receptors for IgG(Tnon-γ cells).
Antibody-Dependent Cellular Cytotoxicity Effector Cell Capability among Normal Individuals
Authors: Edwards David L. , Avis Frederick P. 
Published: December 2022

Abstract
Nonadherent peripheral blood lymphocytes (PBL) from 110 normal individuals were evaluated for their capability to mediate antibody-dependent cellular cytotoxicity (ADCC) against rabbit antibody-sensitized chicken erythrocytes (CRBC). Titration of PBL against a constant number of chromium-51 labeled CRBC allowed for construction of dose response cytotoxicity curves where percent chromium release was plotted against the number of PBL. From these curves the maximum degree of lymphocyte-mediated cytotoxicity and the number of lymphoid cells required for 50% of the maximum lymphocyte-mediated cytotoxicity were determined. The results suggested that in this system the cytotoxic capability of PBL from normal individuals was independent of the age and sex of the donor. The cytotoxic capability of PBL was also found to be constant in individuals tested sequentially. However, significant differences were found to exist between different individuals in their capability of mediating ADCC in this system.