bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE PRODUCTION OF VESICULAR STOMATITIS VIRUS BY ANTIGEN- OR MITOGEN-STIMULATED LYMPHOCYTES AND CONTINUOUS LYMPHOBLASTOID LINES
Authors: Nowakowski Maja , Feldman Joseph D. , Kano Shogo , Bloom Barry R. 
Published: June 2004

A variety of lymphoid cell populations were examined in terms of their ability to replicate vesicular stomatitis virus (VSV), a lytic, RNA-containing virus maturing at the cell surface. The number of cells capable of producing VSV was estimated in terms of infectious centers by the virus plaque assay (VPA), and morphologically by electron microscopy (EM). The lymphoid cells examined in this study included: (a) lymph node cells from delayed hypersensitive guinea pigs stimulated by specific antigen, (b) mouse spleen cells activated by selective bone marrow-derived (B) cell and thymus derived (T) cell mitogens, and (c) cells of human and murine continuous lymphoblastoid or lymphoma lines.
In unstimulated cultures of guinea pig lymph node cells there is a background of approximately 1 in 1,000 cells which produces VSV; in purified protein derivative (PPD)-stimulated cultures the number of cells producing virus was 1.6% in the VPA and 1.9% by EM. These cells were large lymphocytes with some morphological features of transformed lymphocytes but were not typical blast cells. A few macrophages were associated with virus in both stimulated and control cultures. These observations indicate that (a) cells responsive to antigens, as detected by a marker virus, were lymphocytes; (b) cells other than lymphocytes (macrophages) were capable of replicating VSV even without antigenic stimulation; and (c) the correlation of results obtained by VPA and morphologic examination was usually quite good.
Of the total number of mouse spleen cells stimulated with concanavalin (Con A), a T cell mitogen, 4.5 (EM)–5.7% (VPA) were associated with VSV. These were characteristic transformed lymphocytes, similar to phytohemagglutinin (PHA)-stimulated human lymphocytes. In contrast Escherichia coli lipopolysaccharide (LPS)-treated mouse spleen cultures contained lower numbers of virus plaque-forming cells. The majority of such cells associated with virus displayed extensive rough endoplasmic reticulum.
Two cultured murine lymphomas containing lymphocytes with the θ surface marker (L5178Y and EL-4) showed a 15–100-fold higher incidence of virus-producing cells than leukemias (L1210 and C57Bl/6) which did not carry this marker. Similarly, the L2C guinea pig leukemia, a known B cell leukemia, yielded a low percent of virus plaque-forming cells (&lt;2%). However, MOPC-104, a plasma cell tumor presumed to be of B cell origin, was found to be an efficient virus producer. There was a wide variation in the efficiency of VSV replication among human lymphoblastoid lines. One line, Wil-2, produced 80% infectious centers after 24 h of exposure to VSV, and all cells were associated with virus at the EM level. The relationship between the virus-producing cells and different lymphocyte subpopulations as well as the efficiency of the two assays for studying virus-producing lymphocytes is discussed.
BLOCKING AND REDISTRIBUTION ("CAPPING") OF ANTIGEN RECEPTORS ON T AND B LYMPHOCYTES BY ANTI-IMMUNOGLOBULIN ANTIBODY
Authors: Roelants Georges , Forni Luciana , Pernis Benvenuto 
Published: June 2004

Antigen-binding T and B lymphocytes were studied by combined autoradiography and immunofluorescence; mouse spleen lymphocytes binding the antigens, [125I]MSH or [125I]TIGAL, were incubated with rhodamine-labeled anti-Ig reagents or with a rhodamine-labeled IgG fraction of anti-θ serum. B cells were identified as Ig+ or θ-, T cells as Ig- or θ+.
It was found that: (a) 20% (1–2 mo after priming) to 30% (3.5–4 mo after priming) of the antigen-binding cells were T cells. (b) The range of antigen molecules bound by B and T cells was similar. (c) Binding of antigen to B and T cells was inhibited by polyvalent anti-Ig, anti-µ, or anti-L reagents. Binding to T cells was more readily inhibited than to B cells. Normal rabbit serum, antimouse lymphocyte serum, or anti-θ did not inhibit antigen binding. (d) When Ig at the surface of B cells was induced, by noninhibiting concentrations of anti-Ig reagents, to redistribute into polar caps and the cells subsequently exposed to [125I)antigen under noncapping conditions, the [125I]antigen silver grains were distributed in caps superimposed on the Ig fluorescent cap. Of crucial importance, antigen was found in cap in the same proportion of T cells as B cells. Significant capping of antigen receptors was not induced in B or T cells with normal rabbit serum or by anti-Ig reagents absorbed with mouse Ig.
The main conclusions of this series of experiments using direct visualization of antigen-binding B and T lymphocytes is that T cells have antigen-specific receptors, probably of IgM nature, and that the number of these receptors appears to range in the order of thousands.
RELATION OF CHROMOSOME 4 (LINKAGE GROUP VIII) TO MURINE LEUKEMIA VIRUS-ASSOCIATED ANTIGENS OF AKR MICE
Authors: Ikeda H. , Stockert E. , Rowe W. P. , Boyse E. A. , Lilly F. , Sato H. , Jacobs S. , Old L. J. 
Published: June 2004

Genes specifying or controlling the expression of GIX (cell surface), GCSA (cell surface), and gs (internal viral) antigens are located in chromosome 4 (linkage group [LG] VIII) of the AKR mouse.
All three antigens may exhibit mendelian inheritance, mice being antigen positive or antigen negative, but each may also appear in leukemic cells of mice whose inherited genotype was antigen negative. The GIX-determining gene in LG VIII of AKR mice apparently is equivalent to Gv-1, which determines expression of the same antigen in 129 strain mice, but which in the latter strain is located in LG IX. As the estimated distance of Gv-1 from H-2 in 129 mice is considerable (37 units) further tests are now indicated to assess the possibility of pseudolinkage in this case.
The Fv-1 locus, also located in LG VIII, influences the mouse's titer of MuLV, and might thereby be thought to regulate the GIX and gs phenotypes of AKR backcross segregants. But the data indicate a discrete LG VIII locus for GIX, since expression of this antigen is mendelian and independent of infectious virus titer. Since the GIX and GCSA phenotypes of AKR backcross segregants were invariably concordant, these two antigens must be specified or controlled by closely linked genes, and the latter also is presumably independent of virus titer. The question as to what extent expression of gs antigen in the segregants is secondary to virus production is undecided.
CRITICAL ROLE OF DETERMINANT PRESENTATION IN THE INDUCTION OF SPECIFIC RESPONSES IN IMMUNO-COMPETENT LYMPHOCYTES
Authors: Katz David H. , Unanue Emil R. 
Published: June 2004

A detailed analysis of the role of determinant presentation in the process of triggering immunocompetent lymphocytes has been made utilizing cell-bound hapten-carrier conjugates to elicit secondary antihapten antibody responses, primarily in vitro. The results of these experiments demonstrate that: (a) hapten-protein conjugates will attach to the surface membranes of macrophages directly, in the absence of specific antibodies, in a highly immunogenic form; (b) such macrophage-bound conjugates serve as remarkedly efficient stimuli to trigger both thymus-derived (T) and bone marrow-derived (B) cells in a specific manner, lowering the optimal threshold antigen dose (in molar terms) by several logs as compared with soluble antigen; (c) the macrophage is not unique in this regard, since fibroblasts are essentially comparable in the capacity to present antigen in highly immunogenic form; (d) cell surface-bound antigen clearly favors secondary in vitro responses of the IgG as compared with the IgM antibody class; (e) in terms of triggering B or T cells, antigen bound to macrophages in the form of immune complexes does not appear to possess any appreciable advantage over equimolar quantities of directly attached antigen; (f) the increased immunogenicity of cell-bound antigen appears to reflect certain crucial, and undefined, features of cell surface membranes and not merely the stabilization of determinants on a relatively immobile surface; and (g) although the efficiency of lymphocyte triggering is markedly enhanced by cell-bound antigen, the presence of macrophages is apparently not an absolute requirement for eliciting secondary in vitro antibody responses to soluble hapten-protein conjugates.
The relevance of these observations to the nature of the signal induced upon antigen interaction by specific lymphocytes and the sequential cellular events involved in the regulatory influence of activated T cells on B cell responses to antigen is discussed. We postulate that T lymphocytes are best triggered by cell-bound antigen and that after this step the activated T lymphocytes regulate the triggering of B cells with antigen.
BIOLOGICAL CHARACTERISTICS OF T AND B MEMORY LYMPHOCYTES IN THE RAT
Authors: Strober Samuel , Dilley Jeanette 
Published: June 2004

The adoptive secondary antibody response of rats to the hapten-protein conjugate dinitrophenyl-diphtheria toxoid (DNP-DT) was used to investigate the migratory properties and rate of formation of T and B memory cells in the spleen. The experimental findings show that hapten (DNP-BSA)- and carrier (DT)-primed spleen cells act synergistically in the restoration of the adoptive anti-DNP response. Passage of both hapten- and carrier-primed spleen cells through an intermediate host (intravenous injection and subsequent collection in the thoracic duct lymph) showed that both cell types are able to recirculate from the blood to the lymph. In addition, memory to the hapten or carrier could be withdrawn from the spleen by prolonged thoracic duct drainage.
The rate of formation of hapten- and carrier-primed spleen cells was studied by treating donors with [3H]thymidine for 48 h before cell transfer in an attempt to "suicide" rapidly dividing cells. Only a slight reduction in the adoptive response to the hapten or carrier was noted upon transfer of treated cells to irradiated hosts. In further experiments, the cell lineage of hapten- and carrier-primed cells was determined by treating each cell type in vitro with rabbit antirat B cell serum (RARBS) and complement. Although treatment with RARBS did not affect the adoptive response restored by carrier-primed cells, the same treatment abolished the response restored by hapten-primed cells.
These findings indicate that T and B memory cells in the spleen of the rat are relatively long-lived, recirculating lymphocytes. The contribution of fixed or rapidly turning over cells to immunological memory is small or negligible as compared with the latter cells.
ACTIVE SUPPRESSION OF IMMUNOGLOBULIN ALLOTYPE SYNTHESIS
Authors: Herzenberg Leonore A. , Chan Eva L. , Ravitch Myrnice M. , Riblet Roy J. , Herzenberg Leonard A. 
Published: June 2004

Thymus-derived cells (T cells) that actively suppress production of IgG2a immunoglobulins carrying the Ig-1b allotype have been found in adult (SJL x BALB/c)F1 mice exposed to anti-Ig-1b early in life. The suppression is specific for Ig-1b. The allelic product, Ig-1a, is unaffected.
Spleen, lymph node, bone marrow, or thymus cells from suppressed mice suppress production of Ig-1b by syngeneic spleen cells from normal F1 mice. When a mixture of suppressed and normal cells is transferred into lethally irradiated BALB/c mice, there is a short burst of Ig-1b production after which Ig-1b levels in the recipient fall rapidly below detectability. Pretreatment of the cells from the suppressed mice with antiserum specific for T cells (anti-Thy-1b) plus complement before mixture destroys the suppressing activity.
Similar results with suppressor cells were obtained in vitro using Mishell-Dutton cultures. Mixture of spleen cells from suppressed animals with sheep erythrocyte (SRBC)-primed syngeneic normal spleen before culture suppresses Ig-1b plaque-forming cell (PFC) formation while leaving Ig-1a PFC unaffected. Treatment of the suppressed spleen with anti-Thy-1b before transfer removes the suppressing activity.
REGULATION OF THE SECONDARY ANTIBODY RESPONSE IN VITRO
Authors: Ambrose Charles T. 
Published: June 2004

A material inhibiting antibody synthesis in vitro is produced during the productive phase by rabbit lymph node organ cultures undergoing a secondary response. This antibody inhibitory material (AIM) has been isolated from serum-free medium taken from the cultures and also extracted from lymph node fragments as late as their 4th wk in vitro.
AIM inhibits most strikingly the early productive phase of the secondary response in vitro (i.e, during the 2nd wk). AIM isolated from cultures undergoing a given immune response inhibits the same as well as different responses, thus indicating an immunologically nonspecific effect.
Ultrafiltration and related studies reveal that the molecular size of AIM is 10,000–50,000 daltons and that it is not antibody. AIM can readily be separated from 7S globulin by use of CM-cellulose. The inhibitory activity of AIM is lost by digestion with ribonuclease. Thus the avoidance of serum with its high levels of ribonucleases may be crucial in the study of this material.
The presence in eukaryotic cells of metabolic regulators, governors, etc. has been postulated largely by analogy with microbial systems (27). There is little direct evidence about the chemical nature of these presumed regulators. Our data on the RNase sensitivity of AIM raises the possibility in this lymphoid system of regulation by a species of RNA.
MECHANISMS IN THE SUPPRESSION OF DELAYED HYPERSENSITIVITY IN THE GUINEA PIG BY 6-MERCAPTOPURINE
Authors: Phillips S. Michael , Zweiman Burton 
Published: June 2004

The mechanism of suppression, of delayed hypersensitivity to tuberculoprotein by 6-mercaptopurine (6-MP) was studied in guinea pigs. Under the conditions of the protocol, suppression of tuberculin delayed skin test reactivity was not associated with a significantly altered end-organ response to mediators of permeability. No significant alteration of in vivo lymphoid activity, as measured by reconstitution studies, was found. In addition, lymphoid cells from 6-MP-treated animals reacted in a fashion similar to those of placebo-treated animals with respect to (a) antigen-induced lymphocyte proliferation, (b) antigen-induced liberation of macrophage inhibitory factor activity, (c) direct inhibition by antigen of peritoneal exudate cell migration.
Conversely, suppression was seen in levels of blood monocytes and in vitro function of macrophages from 6-MP-treated animals in several respects: (a) adherence to glass, (b) migratory rate, (c) phagocytic capacity. Therefore, it would appear that a ma]or mechanism of 6-MP-induced suppression of delayed hypersensitivity is through its action on effector cells.
IN VITRO INDUCTION OF TUMOR-SPECIFIC IMMUNITY
Authors: Wagner Hermann , Röllinghoff Martin 
Published: June 2004

Induction of tumor-specific immunity in vitro was accomplished by cocultivation of cortisone-resistant murine thymocytes or spleen cells with irradiated syngeneic plasma cell tumors (PCT). The cytotoxic activity generated could be detected in a short-term 51Cr-release assay. Optimal cytotoxic activity against PCT-associated transplantation antigens (TATA) was generated after 7 days in culture. Unlike cytotoxic responses to tumor allografts in which the cytotoxic activity was directed against allogeneic transplantation antigens, the cytotoxic activity obtained in the syngeneic tumor system was specific to the immunizing syngeneic PCT.
Similar parameters of induction of cytotoxic responses in in vitro tumor allograft responses and in the syngeneic tumor system suggested that both reactions are cell-mediated cytotoxic immune responses. With regard to the magnitude of cytotoxic responses obtained, allogeneic transplantation antigens induced about a 30-fold higher cytotoxic immune response than plasma cell TATA. The results are consistent with the concept that in vitro tumor allograft responses and in vitro responses against TATA of PCT are similar in quality, but differ in the magnitude of the cytotoxic response provoked.
SUPPRESSION OR AUGMENTATION OF THE ANTIHAPTEN RESPONSE IN MICE BY ANTIBODIES OF DIFFERENT SPECIFICITIES
Authors: Haughton G. , Mäkelä O. 
Published: June 2004

We have measured the production by (C57 x CBA)F1 mice of hapten-binding antibody in response to a standard dose of 50 µg of alum-precipitated NIP12-CG and the influence on this response of the prior administration of hyperimmune antisera raised against the homologous conjugate, the carrier globulin alone, the hapten conjugated to a non-cross-reactive carrier (NIP4-OA), or a related hapten (NP) coupled to CG.
The homologous antiserum was strongly immunosuppressive; a dose capable of binding about 1% of the administered hapten caused significant suppression. High doses of anticarrier serum caused significant but modest suppression (about 50%); low doses had no effect. High doses of the serum prepared against NIP4-OA suppressed the 19 day response by more than 97%, while 100–1,000 times lower doses caused the response to be elevated to about double the control level. The antibodies responsible for immunosuppression could be removed from this serum, as could the NIP-binding antibodies, by absorption with NIP coupled through ethylenediamine to insoluble Sepharose. The ability of this serum to augment the response was not reduced by such absorption. Augmenting antibodies could be removed by absorption with HOP-BSA-Sepharose. Thus, immunosuppression and augmentation are functions of two different populations of antibody. The former are specific hapten-binding antibodies, the latter seem to be directed against new antigenic determinants created by coupling any of the family of haptens through lysine to protein carriers. In support of this contention, it was observed that rabbit antiserum to NP-CG, after absorption with CG-Sepharose, augmented the response of mice to standard immunization with NIP12-CG.
Female mice produced significantly more NIP-binding antibody than did males.
TEMPERATURE-DEPENDENT VARIATION IN THE SYNTHESIS OF GROUP-SPECIFIC CARBOHYDRATE BY STREPTOCOCCAL VARIANT STRAINS
Authors: Ayoub Elia M. , Dudding Burton A. 
Published: June 2004

A temperature-dependent alteration in the synthesis of the group-specific polysaccharide was found to occur in two "variant" streptococcal strains, A-486-Var and C 121/46/4. These strains synthesize a polysaccharide with variant immunochemical characteristics when grown at 37°C. However, when these organisms are grown at lower temperatures, 22°C, an enhanced synthesis of Group A carbohydrate occurs. Other variant strains show no appreciable alteration of the cell wall carbohydrate composition when grown at lower temperatures. Studies on an intermediate strain show that this organism has a propensity for the synthesis of a polysaccharide with higher glucosamine content and enhanced Group A serological reactivity when grown at 22°C.
Immunochemical studies performed on the carbohydrates produced by the A-486-Var at various temperatures revealed that the appearance of Group A serological reactivity at lower temperatures is due to the additional synthesis of a polysaccharide with Group A specificity along with the continued synthesis of a variant carbohydrate. This finding contrasts with data obtained on the carbohydrate produced by the intermediate organisms that appears to consist predominently of one molecule bearing dual A and variant antigenic determinants.
MUTANTS OF NONPRODUCER CELL LINES TRANSFORMED BY MURINE SARCOMA VIRUS
Authors: Hatanaka M. , Klein R. , Long C. W. , Gilden R. 
Published: June 2004

Tumorigenic and nontumorigenic mutants induced by a single 5'-bromodeoxyuridine (BrdU) treatment of a nonproducer (NP) tumorigenic cell line were isolated and characterized. Among the cloned derivatives were examples of virus-free and sarcoma virus-producing cell lines. Oncogenicity did not correlate with production of virus or ease of rescue of the sarcoma genome. All lines, including nononcogenic derivatives, retained the sarcoma genome.
Phenotypic reversion of some cell mutants was observed after in vivo inoculation or long term in vitro cultivation. The M-50T cell line, obtained from a tumor induced by M-50 cells, had a sarcoma genome rescuable by direct superinfection; this was only achieved with parental M-50 cells by a cell fusion rescue technique. The M-43-2T cell, obtained from a single small static tumor induced by otherwise nononcogenic M-43-2 cells, shed sarcoma virus and became tumorigenic. M-58-4-48 became tumorigenic after passage 48 of the M-58-4 line, which was originally nontumorigenic. These observations of phenotypic reversion demonstrate that the presence of the sarcoma gene in cells is an essential but not sufficient condition of tumorigenesis.
THE MEMBRANE ATTACK MECHANISM OF COMPLEMENT
Authors: Kolb William P. , Müller-Eberhard Hans J. 
Published: June 2004

The membrane attack mechanism of complement, C5 to C9, has previously been postulated to associate on the target cell surface to a stable decamolecular complex with a calculated mol wt of 995,000.
A soluble and stable complex consisting of C5, C6, C7, C8, and C9 has now been demonstrated to arise as a consequence of complement activation by the classical or alternate pathway. It has a sedimentation coefficient of 22.5S and a mol wt of 1 million daltons, and it migrates on electrophoresis at pH 8.6 as an α-globulin.
The stable and soluble C5b-9 complex cannot bind to erythrocytes and has no demonstrable cytolytic activity. However, due to partially unsaturated binding sites for C9, it can bind additional C9 and thus function as an inhibitor of lysis of EAC1-8 by C9.
These results support the concept according to which the membrane-bound attack system of complement represents a stable, decamolecular assembly of C5b-9. Unlike its analogue in free solution, the membrane-bound complex is cytolytically active.