bluuebunny/crossref_metadata_2025 huggingface dataset:
The Number of Reactive Cells in Mouse Lymphocyte Cultures Stimulated by Phytohemagglutinin, Concanavalin a or Histocompatibility Antigen
Authors: Jones G.
Published: December 2022

Mouse lymphocytes were cultured with phytohemagglutinin, concanavalin A, or allogeneic cells. The number of cells entering DNA synthesis was determined by pulse labeling with tritiated thymidine at various times. Phytohemagglutinin induced 11 to 26% of the initial population to enter the proliferative cycle over 1 to 4 days. Concanavalin A induced 29 to 46% of the initial population to enter proliferation over 1 to 5 days. In mixed leukocyte cultures approximately 1% of BALB/c or CBA lymphocytes responded to F1 cells over 1 to 5 days and in two-way mixed cultures between BALB/c and CBA cells a similar proportion, 1% of the initial population, responded. Variations in the total cell concentration or the ratio of parental to F1 cells in mixed leukocyte cultures produced no change in the percentage of reactive cells. The number of reactive cells was increased approximately 7-fold, nearly 8% of the initial population, in BALB/c mice that had been pre-sensitized with F1 cells. These findings are discussed in relation to the recognition of antigen by thymus derived lymphocytes.
Xenogeneic Reactivity of Human Fetal Lymphocytes
Authors: Asantila Tuula , Sorvari Tapani , Hirvonen Toivo , Toivanen Paavo
Published: December 2022

In a local graft-vs-host reaction under a rat kidney capsule, spleen lymphocytes from 13-week-old human fetuses were capable of a xenogeneic immunologic reactivity. At 18 to 23 weeks of the intrauterine life, the reactivity was of the same magnitude as that of adult human lymphocytes. Fetal thymus cells were less active than fetal spleen cells. The results indicate that immunologic reactivity against xenogeneic cells is a genuine property of virgin unstimulated lymphocytes.
Role of Cyclic AMP in Mitogen Induced Transformation of Human Peripheral Leukocytes
Authors: Krishnaraj R. , Talwar G. P.
Published: December 2022

Phytohemagglutinin (PHA) causes a stimulation of the adenyl cyclase activity of human peripheral leukocytes within 15 min of incubation of cells with the mitogen. An increase in the intracellular content of cyclic 3′,5′-adenosine monophosphate (cAMP) was also observed in purified lymphocyte preparations. The blast transformation and the stimulation of the adenyl cyclase by PHA are dose dependent; excessive concentration of the mitogen is inhibitory for both effects. A variety of pharmacological agents (propranolol; chlorpromazine and imidazole) that interfere with the PHA induced activation of adenyl cyclase or that lower the intracellular levels of cAMP at the early stages inhibit also the blast transformation as measured by the incorporation of 3H-thymidine into DNA on the day of peak response. cAMP however does not simulate fully the mitogenic action of PHA. When added to the medium, a maximal stimulation of about 2- to 3-fold over the basal control value is obtained which is far lower than the transformation with PHA (450-fold). Dibutyryl cAMP, cyclic 3′,5′-guanosine monophosphate and cyclic 3′,5′-cytidine monophosphate were ineffective in the induction of transformation. Moreover, another potent mitogen, concanavalin A, gives only a marginal activation of adenyl cyclase and a moderate increase in intracellular cAMP levels in the initial phases. It is concluded that activation of adenyl cyclase and a rise in intracellular content of cAMP in the early phase are possibly a part (but not all) of the initial effects of PHA on human leukocytes.
Antigen-Induced Inhibition of Experimental Allergic Encephalomyelitis
Authors: Swanborg Robert H.
Published: December 2022

The smaller of the two rat myelin basic proteins (rat-S) was isolated by gel filtration and employed for antigen-induced inhibition of experimental allergic encephalomyelitis (EAE) in guinea pigs. Rat-S lacks a sequence of 40 amino acids which are present in the larger myelin basic protein including part of the major determinant which causes EAE in the guinea pig. The results show that non-encephalitogenic rat-S, given before sensitization with the large basic protein, significantly inhibits EAE in the guinea pig, although the protection provided by the large basic protein is somewhat more complete. These findings suggest that different sites on the basic protein molecule are responsible for the immunologic induction and inhibition, respectively, of EAE.
Early Biochemical Alterations Induced by Lymphotoxin in Target Cells
Authors: Rosenau Werner , Goldberg Melvin L. , Burke Gertrude C.
Published: December 2022

Lymphocyte-mediated target cell destruction apparently involves a cytotoxic protein, lymphotoxin, produced by antigen- or mitogen-stimulated lymphocytes. Various biochemical functions of L cells exposed to purified lymphotoxin were examined. No alterations in glycolysis, oxidative phosphorylation or Na-K pump were observed. Nor does lymphotoxin-induced cytolysis appear to be mediated by lysolecithin. In contrast to these negative findings, an early decrease in the number of polysomes and a marked increase in the rate of RNA synthesis were detected. The cytotoxic effect of lymphotoxin is greatly potentiated and accelerated by actinomycin D, even at early intervals, when this inhibitor per se causes little cytotoxicity. The ability to potentiate the effect of lymphotoxin would be particularly important in tumor immunity, where accentuation of the relatively weak immune resonse might be beneficial to the host.
Demonstration of Antibodies to Deoxyribonucleic Acid by Counterelectrophoresis
Authors: Klajman A. , Farkash Ruth , Myers B. D.
Published: December 2022

Counter electrophoresis (CEP) was used to demonstrate the presence of antibodies to DNA in the sera of patients suffering from systemic lupus erythematosus. The method described is rapid, simple, easy to perform, and sensitive. Washington the agar slides in saline on completion of CEP is of great importance, as a number of lines resembling the precipitating lines disappear after washing.
Relationship between Proliferative and Effector Phases of the Mixed Lymphocyte Reaction and Graft-Vs-Host Reaction
Authors: Howe Michael , Berman Lee , Cohen Lewis
Published: December 2022

Spleen and thymus cells from BALB mice were shown to undergo proliferation in the mixed lymphocyte reaction and graft-vs-host reaction in response to antigens of H-2 identical DBA mice without generating effector lymphocytes exhibiting specific cytotoxicity for DBA target cells. Both proliferation and generation of cytotoxicity occurred when BALB lymphocytes were exposed to antigens of H-2 non-identical CBA mice. The proliferative response of BALB thymocytes to CBA antigens greatly exceeded that of BALB spleen cells, even though the generation of cytotoxic lymphocytes was greater in the spleen population. These data suggest that the proliferative and effector phases of the mixed lymphocyte reaction and the graft-vs-host reaction may be mediated by separate lymphoid cell populations having differing antigen requirements for activation.
T Cell Surface Markers on Lymphoblasts from Acute Lymphocytic Leukemia
Authors: Borella Luis , Sen Luisa
Published: December 2022

This report provides the first evidence that lymphoblasts from different patients with acute lymphocytic leukemia (ALL), which are indistinguishable by cytomorphology, have membranes with different properties, such as the presence of thymus dependent (T) cell surface markers. In this study T cells were determined by spontaneous rosette formation with sheep erythrocytes and B (thymus-independent) cells by immunofluorescence of surface immunoglobulins. Of four children with untreated ALL, one had 62% lymphoblasts with T markers in bone marrow. Neoplastic cells with T markers were absent in the other three. None of these patients had lymphoblasts with B markers. In contrast, B and T lymphocytes were present in the blood and bone marrow of 24 children with ALL in remission and off therapy. None of these children had a mediastinal mass, but analysis of initial clinical manifestations suggested a more aggressive or extensive disease in the patient with T lymphoblasts. These data indicate that in some patients with ALL the neoplastic cells may be of thymic origin.
Thymus Independent Stimulator Cells in The Mixed Lymphocyte Reaction
Authors: Harrison Michael R.
Published: December 2022

The proliferative response of allogeneic lymphocytes cultured together, the mixed lymphocyte reaction (MLR),2 has been widely used as an in vitro correlate of the antigen recognition phase of the homograft response. Recent studies in mouse and man suggest that the structures responsible for MLR activation are largely coded for by genes which are within the major histocompatibility complex (MHC) of the species (1, 2), but are distinct from the genes controlling the serologically defined major histocompatibility determinants (3, 4). However, the nature and cellular distribution of the gene products which actually mediate recognition of one cell (the target cell) by another cell (the responder cell) is not well understood.

The “recognizing” structure is likely to be a specific receptor present on thymus derived (T) lymphocytes since T cells are generally required as responder cells in the MLR (5–7).
Complement Receptors on Cell Membranes
Authors: Okada Hidechika , Nishioka Kusuya
Published: December 2022

On DEAE-cellulose column chromatography, two fractions were obtained from mouse plasma. One made EA(IgM)C42 reactive to human erythrocytes but not to Daudi cells, a cultured cell line derived from Burkitt lymphoma. The addition of the other fraction to these intermediate complexes of complement on cells diminished adherence to human erythrocytes but generated adherence to Daudi cells. From these results we conclude that the receptors on human erythrocytes and on Daudi cells react differently with the intermediate complexes of complement.
Analysis of Antibody Populations to Oligo-Alanine Determinants
Authors: Kolb Hubert , Weiler Eberhardt
Published: December 2022

A method is described for the quantitative measurement of IgG subclasses IgG1 and IgG2a in antibody to oligo-D-alanine produced by individual mice. This was made possible by the use of subclass-specific anti-allotype sera as facilitating reagents in an indirect hemolysis system. Thus in heterozygous mice subclasses as well as both parental allotypes can be distinguished. Among antisera tested, the proportion of IgG1 and IgG2a varied with the individual mouse; either IgG1 or IgG2a may be predominant.
Lymphocyte Populations of AKR/J Mice
Authors: Zatz Marion M. , Goldstein Allan L. , White Abraham
Published: December 2022

The present study describes changes which occur in the lymph nodes, spleen, and thymus lymphocytes of aging AKR/J mice. Lymphocytes from mice between 3 and 14 months of age were investigated with respect to three thymus-dependent properties, i.e., in vivo homing to lymph nodes, responsiveness to phytohemagglutinin, and expression of the θ AKR antigen. Decreases in the numbers of lymph node-seeking, recirculating lymphocytes in lymph node, spleen, and thymus, and diminished responsiveness of spleen cells to stimulation by phytohemagglutinin were observed with increasing age. No change in the sensitivity of lymph node cells to anti-θ serum was noted in the aging AKR/J mice.

The significance of the decline in the size of the thymus-dependent recirculating lymphocyte pool with age is considered in relation to the concomitantly occurring onset of spontaneous lymphocytic leukemia, which is characteristic for the AKR/J strain.
Lymphocyte Populations of AKR/J Mice
Authors: Zatz Marion M. , White Abraham , Goldstein Allan L.
Published: December 2022

The present study describes abnormalities that occur in the lymph node, spleen, thymus, and blood lymphocytes of two distinct types of leukemic AKR/J mice. These two types, designated A and B leukemia, occur in a ratio of 3:1 in mice aged 7 to 10 months. Type A leukemic mice are characterized by the presence of a thymoma and enlarged peripheral lymphoid organs, and lymphocytes which 1) fail to migrate to lymph nodes, 2) exhibit normal transformation in response to PHA, and 3) have elevated sensitivity to anti-theta (θ) serum. Type B leukemic mice have an atrophic thymus and elarged peripheral lymphoid organs; their lymphocytes 1) fail to home to lymph nodes, 2) exhibit decreased transformation in response to PHA, and 3) have decreased sensitivity to anti-θ serum. The significance of the dissociation of thymus-dependent characteristics, e.g., lymphocyte recirculation, response to PHA, and expression of the θ antigen, observed in type A leukemic lymphocytes, as well as the possible origins of type A and B leukemic lymphocyte populations, are discussed.
Identification of J-Chain in Polymeric Immunoglobulins from a Variety of Species by Cross-Reaction with Rabbit Antisera to Human J-Chain
Authors: Kobayashi Kunihiko , Vaerman Jean-Pierre , Bazin Hervé , Lebacq-Verheyden Anne-Marie , Heremans Joseph F.
Published: December 2022

Two rabbit antisera, rendered specific for human J chains, were shown to cross-precipitate extensively with J chains of completely reduced and alkylated polymeric immunoglobulins (IgA, IgM, and/or SIgA) from the dog, cat, cow, goat, sheep, pig, horse, hedgehog, guinea pig, rat, mouse, and chicken. The data emphasize the great evolutionary stability of the J polypeptide chain.
Selective Activation of Chicken T Lymphocytes by Concanavalin A
Authors: Toivanen Paavo , Toivanen Auli
Published: December 2022

In vitro response to Con A of chicken spleen lymphocytes was reduced by thymectomy carried out at hatching and completed by irradiation. Bursectomy combined with irradiation was ineffective. The effect of thymectomy was partially reversed by transplantation of thymus cells from 10-week-old donors although transplantation of bursa cells had no effect. These findings indicate that, also in the chicken, Con A is selectively a T cell mitogen.
Relationship between Graft-vs-Host Reactivity and Possession of the High Leukemia Genotype hr/hr
Authors: I'Anson Valerie A. , Gasser David L.
Published: December 2022

The immunologic reactivity of hr/hr and hr/ + mice of the HRS strain was studied by the graft vs host (GVH) assay. Spleen cells from hr/+ donors caused significantly greater GVH reactions than did spleen cells from hr/hr mice. These results suggest that genetically determined immunologic hyporesponsiveness may contribute to the high leukemia susceptibility of hr/hr mice.
Characterization of Glass Adherent Human Mononuclear Cells
Authors: Koller Charles A. , King Gerald W. , Hurtubise Paul E. , Sagone Arthur L. , LoBuglio Albert F.
Published: December 2022

Although adherence to glass is commonly used to prepare monocyte monolayers from blood mononuclear cell suspensions (1–3), several recent reports suggest that lymphocytes are also able to adhere to either glass or glass substitutes like nylon or tissue culture dishes (4, 5). Using morphologic criteria, Levis (4) reported considerable lymphocyte binding to glass coverslips placed in mononuclear cell suspensions. Although many of the lymphocytes could be detached by rigorous mechanical washing, this resulted in a loss of monocytes as well. Rosenthal (5) has suggested that adherence to glass can be used to deplete selectively lymphocyte preparations of antibody-forming or “bursal-derived” (B)2 lymphocytes. Similarly, Boldt (6) has demonstrated that nylon columns can remove from a suspension of blood mononuclear cells a population of lymphocytes which are “highly responsive” to concanavalin A. These observations indicate that monocyte monolayers prepared by adherence of blood mononuclear cells to glass or tissue culture dishes may be contaminated by considerable numbers of lymphocytes.
The Stoichiometry of J Chain in Human Secretory IgA
Authors: Halpern Michael S. , Koshland Marian Elliott
Published: December 2022

Quantitative methods were developed to measure the J chain content of the polymeric immunoglobulins. The methods involved two steps: first, isolation of a light-J chain fraction, and second, determination of the ratio of the two chains in the fraction from differences in amino acid content. When these methods were applied to human colostral IgA, the dimers were found to contain one mole of J chain for every two monomer units while the tetramers contained one J for every four monomer units. This stoichiometry supports the hypothesis that J chain plays an obligatory role in polymer assembly and suggests the function of the J chain is to initiate polymerization by linking two monomer units.
Serum Proteins Involved in Decay and Regeneration of Cobra Venom Factor-Dependent Complement Activation
Authors: Fearon Douglas T. , Austen K. Frank , Ruddy Shaun
Published: December 2022

The development of C3-cleaving and indirect lysis activity in human serum after the introduction of cobra venom factor (CoVF) was associated with an increase in both the apparent molecular weight and the positive charge of CoVF. After decay at 37°C of these CoVF-induced activities, the CoVF reverted to its native state as assessed by these two physical parameters. No functional differences between native CoVF and CoVF reisolated from decayed CoVF-serum mixtures existed with respect to the factors required for indirect lysis (Factors B, D, and E) and C3 destruction (Factors B and D). In decayed CoVF-serum mixtures, properdin Factor B was in its immunoelectrophoretically converted form, and the addition of fresh Factor B restored full indirect lysis activity. Mixtures of CoVF, Factor D, and Factor B in molar excess of CoVF exhibited no loss of CoVF-dependent activity unless the excess Factor B had been utilized or prevented from recycling with CoVF and Factor D. The behavior of Factor B during the formation and decay of the CoVF-dependent, C3-cleaving enzyme was similar to that of C2 in its interactions with C1̄ and C4.
Binding of Maclura Pomifera Lectin to Rat Lymphoid Cells and Erythrocytes
Authors: Jones Joe M. , Feldman Joseph D.
Published: December 2022

Extracts of Maclura pomifera seeds (MP-Ext), which agglutinate leukocytes and erythrocytes of rats and other animals, were labeled with 125I. Labeled extracts were adsorbed to rat cells and eluted (125I-MP) by an excess of D-melibiose, a known inhibitor of the binding of seed extracts. Over 80% of 125I-MP bound to rat cells. Binding was inhibited by carbohydrates related structurally to D-melibiose but not by lactose, glucose, or carbohydrates unrelated to D-melibiose. Thymus cells bound larger quantities of 125I-MP than cells of spleen, bone marrow, or erythrocytes and binding by spleen cells from thymectomized animals was reduced. Thymus cells were also selectively stained by fluor-labeled MP-Ext. 125I-MP, phytohemagglutin, and concanavalin A (Con A) were found to recognize distinct receptors on BN rat cells since they did not compete in binding tests and since they are inhibited by different carbohydrates. Eluted MP was mitogenic for spleen cells in serum-free medium, but not in medium containing serum. In addition, it augmented the mitogenic effects of Con A.
β2-Microglobulin Production in Vitro by Human Hematopoietic, Mesenchymal, and Epithelial Cells
Authors: Evrin Per-Eric , Nilsson Kenneth
Published: December 2022

The capacity of normal and malignant human cells to synthesize β2-microglobulin has been studied in vitro. Quantitative determinations of β2-microglobulin by a radioimmunoassay were performed on culture media harvested from seven freshly explanted lymphoma cells and 37 cell lines of hematopoietic, mesenchymal, or epithelial origin. β2-Microglobulin was detected in all but one lymphoma cell culture. Lymphoma cells, freshly explanted, as well as those of continuously growing lines seem to have a low capacity to synthesize β2-microglobulin while permanent lymphoblastoid lines secrete the protein at approximately the same rate as mesenchymal cells. The highest production rate of β2-microglobulin was observed in some epithelial carcinoma cell lines. No correlation was found between the capacity to synthesize immunoglobulins and β2-microglobulin.
Effect of PPD on the Specific Immune Response to Heterologous Red Cells in Vitro
Authors: Kreisler J. Miguel , Möller Göran
Published: December 2022

Purified protein derivative of tuberculin (PPD) was found to enhance the primary and secondary immune responses in vitro to heterologous red cells in spleen cells from non-BCG-immunized mice. Even though PPD is a bone marrow-derived (B) cell mitogen the enhanced cellular immune response was specific for the antigen added to the cultures. Secondary IgG responses in vitro to sheep red blood cells required a 100-fold lower concentration of PPD for maximal enhancement as compared to the primary IgM plaque-forming cell response.

The presence of adherent cells was required for the synergistic effect between antigen and PPD. The requirement for thymus-derived (T) cells could be partially overcome by PPD, but a full enhancing effect of PPD required the presence of both T cells and macrophages. It is likely that the antigen, but not the PPD, effect requires the presence of the helper cells.

PPD and red cell antigens cooperated in a synergistic rather than an additive fashion when enhancing the specific immune response. In comparison with other B cell mitogens, such as LPS and pneumococcal polysaccharide SIII, PPD was found to be the most effective agent in increasing the primary immune response in vitro.

The findings suggest that a nonspecific B cell mitogen and specific antigen can cooperate in increasing the magnitude of a specific immune response.
Human J-Chain: Isolation and Molecular Weight Studies
Authors: Kang Yoon Se , Calvanico Nickolas J. , Tomasi Thomas B.
Published: December 2022

J-chain was isolated from human IgA, SIgA and IgM by three different procedures. The simplest method was precipitation in water. The molecular weights were studied using two species plot analysis of the sedimentation equilibrium data. Two populations of molecules were found. One had a molecular weight of 13,300 to 17,700 and the other 6,400 to 11,500. These data are compared with those obtained by other investigators.
Induction of Experimental Autoallergic Sialadenitis
Authors: White Stuart C. , Casarett George W.
Published: December 2022

An experimental autoallergic sialadenitis of the submandibular glands of the Lewis rat has been induced by immunization with allogeneic submandibular gland homogenate and adjuvants. The severity, incidence and duration of the of the lesion were significantly greater when female allogeneic submandibular gland donors were sexually mature rather than sexually immature. Passive transfer of lymph node cells and/or serum from immunized animals with severe lesions into histocompatible recipients rarely induced lesions in the recipients.
Studies on IgA and IgG Monoclonal Proteins Derived from a Single Patient
Authors: Fair D. S. , Krueger R. G. , Gleich G. J. , Kyle R. A.
Published: December 2022

The serum from a patient (GR) with multiple myeloma was shown to contain two unique homogenous bands by cellulose acetate electrophoresis. These components were further identified as a monoclonal IgG2k and a monoclonal IgAk. Rabbit antisera directed against IgG (GR) and IgA (GR) monomer were absorbed to render them specific for individual antigenic (ind) determinants. Both proteins were capable of inhibiting the reaction between labeled protein and its homologous ind antiserum in the radioimmunoassay indicating that both immunoglobulins shared ind determinants. In addition, the determinants shared between the two proteins appear to be identical. The potential sharing of any two heavy chain constant genes among all heavy chain constant genes is discussed.
Enzymatic Enhancement of Cell-Mediated Cytotoxicity and Antibody-Dependent Cell Cytotoxicity
Authors: Kedar Eli , de Landazuri Manuel Ortiz , Fahey John L.
Published: December 2022

The effects of papain, trypsin, Pronase, neuraminidase, and phospholipase C on in vitro cell-mediated cytotoxicity (CMC) and antibody-dependent cell cytotoxicity (ADCC) have been studied in a syngeneic tumor system. Proteolytic enzyme treatment of lymphoid (effector) cells at low concentrations (<0.1 mg/ml) and for short times (less than 30 min) produced a 2- to 6-fold increase in CMC and ADCC. Neuraminidase also augmented both CMC and ADCC, whereas phospholipase C had no effect. The specificity of the cytotoxicity (CMC) amplification following enzymatic treatment was indicated by observations that: a) the activated immune cells were not cytotoxic to unrelated tumor cells, and b) normal cells were not activated.

The enzymatically induced potentiation was observed only with organs which already had demonstrable cytotoxic activity. Kinetic studies indicated that the enzymatic treatment may produce a quantitative as well as a qualitative change in the lymphoid cell population. Enzymatic treatment of lymphoid cells may be a valuable means of increasing the sensitivity of in vitro assays for cell-mediated immunity.

Pretreatment of lymphoid cells with high enzyme concentrations (over 1 mg/ml) or for prolonged periods of time (over 1 hr) did not reduce ADCC, but strongly suppressed CMC. This difference in response to proteolytic enzymes emphasizes chemical differences in the membrane components responsible for CMC vs ADCC.
IgM Anamnestic Immune Response to the Haptenic Determinant DNP on a Thymus-Independent Carrier
Authors: del Guercio Paolo , Thobie Nicole , Poirier Marie France
Published: December 2022

Antibody formation in mice against a haptenic determinant such as dinitrophenyl (DNP),3 is strictly related to the immunogenicity and nature of the carrier. Thus, a carrier that interacts only with non-thymus-derived (B) lymphocytes, e.g., levan (LE) (1), induces in vivo a thymus-independent primary response to DNP (2). The DNP-LE conjugate produces only IgM antibody against DNP (2), and the response is not potentiated by Freund's adjuvants (3). This report describes the anamnestic response to the DNP-LE conjugate.

LE with the reduced molecular weight of 100,000 was coupled to DNP, as previously described (2). Male CBA mice (20 to 25 g) were injected i.v. with different doses of DNP6-LE. Sixteen weeks later mice were challenged i.v. with 10 µg of DNP6-LE. In transfer experiments CBA mice were primed i.v. with 100 µg of DNP6-LE, and 1 or 4 weeks later their spleens were removed and homogenized in medium 199 (4).
Ontogeny of Peyer's Patches and Immunoglobulin-Containing Cells in Pigs
Authors: Chapman Harold A. , Johnson John S. , Cooper Max D.
Published: December 2022

The embryonic development of intestinal lymphoid tissue and immunoglobulin-containing cells (µ-, γ- and light chain determinants) was examined in 55 porcine fetuses. Lymphoid cells in a characteristic follicular distribution were found in Peyer's patches as early as 50 days of gestation, but detection of Peyer's patches from 50 to beyond 70 days of gestation required microscopic examination of serial sections of the intestines. The size of the intestinal lymphoid follicles steadily increased during gestation, but cortico-medullary division was not observed until after birth. IgM-containing cells were first seen in 55-day spleens and were followed by IgG-containing cells in the thymus 10 to 15 days later. These observations are interpreted as support for the hypothesis that the lymphoid follicles in Peyer's patches are mammalian bursa-equivalent sites.
Activation of Rat Mast Cells by Low Molecular Weight Stimuli
Authors: Morrison D. C. , Roser J. F. , Henson P. M. , Cochrane C. G.
Published: December 2022

Radiolabeled mast cell activators, compound 48/80, and a cationic protein from neutrophils were shown to bind almost exclusively to mast cells in suspensions of rat peritoneal cells. A correlation was obtained between the binding of activator and release of 3H-serotonin at low concentrations of activator. It was shown that activator binding was substantially enhanced by the release process itself, thus demonstrating that release of amines exposes new sites for binding of activator. Saturation binding studies using compound 48/80 indicated that approximately 6×1010 molecules of activator could be bound per mast cell under conditions in which release of vasoactive amines occurs. A third mast cell activator, polymyxin B, was shown to compete with compound 48/80 for binding to mast cells.

A technique has also been described for determining accurately the release of amines from mast cells. 3H-serotonin was incorporated in mast cells in vitro and specifically released by agents which stimulate the cells.
In Vitro Anamnestic Response of Rabbit Lymph Node Cells: Evidence for Cell Collaboration in Induction and Regulation
Authors: Stavitsky Abram B. , Cook Richard G.
Published: December 2022

An in vitro model and a highly specific goat IgG antibody to rabbit thymocytes (ATG) were utilized to determine whether thymus-dependent (T) lymphocytes participated in the anamnestic antibody response. The addition of various amounts of keyhole limpet hemocyanin (KLH) to lymph node cells, primed in vivo with KLH either 6 days or 2 months previously, induced the early synthesis of DNA and RNA, followed by the synthesis of IgM and/or IgG antibody to KLH. This antibody response was highly antigen concentration-dependent: the addition of 10 or 100 µg of KLH induced much less antibody synthesis than 1 µg. When ATG was present in cultures with KLH, the induction of nucleic acid and antibody syntheses was markedly inhibited. Thus it appears that these antigen-induced syntheses are mediated by T lymphocytes, and that in the rabbit the collaboration of T and bursal-equivalent (B) lymphocytes is required for induction of the anamnestic response to KLH. Kinetic analysis indicated that the KLH-induced events, mediated by T lymphocytes and prerequisite for the antibody response, occurred during the 1st day of culture. Evidence was also obtained that T lymphocytes were involved in the nonspecific regulation (enhancement) by normal goat globulin of the antibody response to KLH. The relation of the mechanisms of specific induction to those of regulation of antibody synthesis and the question of how ATG affects these mechanisms were discussed.
Studies on the Species-Variability of Experimental Allergic Encephalomyelitis in Guinea Pigs and Rats
Authors: Swanborg Robert H. , Swierkosz James E. , Saieg Robert G.
Published: December 2022

The present investigation was carried out to compare myelin basic protein (BP) isolated from guinea pig and rat central nervous system with respect to physicochemical properties and ability to induce experimental allergic encephalomyelitis (EAE) in Hartley guinea pigs and Lewis rats. The single BP tryptophan residue was modified with 2-hydroxy-5-nitrobenzyl bromide (benzyl-BP). Polyacrylamide gel electrophoresis at acid pH or in sodium dodecyl sulfate (SDS) revealed that mobility and molecular size, respectively, were not changed by modifying the tryptophan residue. Guinea pig and rat BP, and each respective benzyl-BP, were highly encephalitogenic in rats, as was the purified small rat basic protein (rat-S). However, the peptide derived from the N-terminal end of the BP molecule by cyanogen bromide cleavage (CB-1) was completely inactive in rats. Guinea pig and rat BP were also highly encephalitogenic in guinea pigs, but the benzyl-BP preparations were relatively inactive. Rat-S and CB-1 were only mildly encephalitogenic. It appears that the determinant which induces EAE in rats is located between BP residues 21 and 115. The guinea pig recognizes at least two disease-inducing sites.
In Vitro Detection of Immune Responses to MTV-Induced Mammary Tumors: Activity of Spleen Cell Preparations from Both MTV-Free and MTV-Infected Mice
Authors: Blair Phyllis B. , Lane Mary Ann , Yagi Mary Jane
Published: December 2022

BALB/cfC3H mice, neonatally infected with mammary tumor virus (MTV), can respond immunologically to MTV-associated antigens on tumor cells: spleen cells from both normal adult females and females which have developed MTV-induced mammary tumors significantly inhibit growth and survival of target tumor cells in culture. Essentially the same level of reactivity is observed in normal BALB/cfC3H females between the ages of 8 and 32 weeks. Tumor-donor spleen cells are considerably more active. An unexpected finding was the observation that supposedly MTV-free BALB/c adult females also possess spleen cells specifically reactive against MTV-induced mammary tumor cells. The only mice tested whose spleen cells were not reactive were BALB/c females younger than 14 weeks of age. BALB/c serum blocked activity of BALB/c but not BALB/cfC3H spleen cells, and BALB/cfC3H serum blocked activity of BALB/cfC3H but not BALB/c spleen cells; thus, the two groups of mice are responding to different MTV-associated antigens on the target cells. Tumor-donors respond to both types of antigens, and also to tumor-specific antigens.
Tumor Induction by Immunologically Activated Murine Leukemia Virus: Cellular Immunity Early in the Graft-vs-Host Reaction
Authors: Ruddle Nancy H. , Armstrong Martine Y. K. , Richards Frank F.
Published: December 2022

Cellular immunity of (BALB/c × A)F1 mice has been examined early after induction of a graft-vs-host reaction (GVHR) by (BALB/c) spleen cells. Previous work has shown that such mice develop murine leukemia virus titers early and lymphomas after a latent period of some months. We wished to determine if an impairment of cellular immune capacity could be associated with these phenomena. When GVHR mice were compared to normals in vivo, skin graft rejection was prolonged slightly across the H2 histocompatibility barrier and somewhat more prolonged across a non-H2 barrier, delayed hypersensitivity to tuberculin was slightly reduced, and rejection of two plasmacytoma tumors was more efficient early and normal later in the GVHR. In vitro, lymphocytes from GVHR mice were normal or hyperreactive as indicated by their normal cytotoxicity against cells expressing skin graft antigens and their heightened sensitivity to tuberculin and A9L cells detected as “nonspecific” cytotoxicity. Thus, in the parameters tested there was no evidence of immune suppression at the level of the cell.
The Role of T Lymphocytes in the Primary Humoral Antibody Response to Brucellin
Authors: Tingle Aubrey J. , Shuster Joseph
Published: December 2022

The relative ability of normal and adult, thymectomized, bone marrow-reconstituted (TxIB) CBA/J mice to produce humoral antibody in response to primary brucellin immunization was assessed over a wide antigen dose range. An analysis was made of the kinetics and immunoglobulin class of the primary humoral antibody response in relation to the immunizing dose of brucellin employed. Antibody responses in T cell deficient (TxIB) mice were characterized by an increase in the threshold dose of brucellin at which antibody production was initially detected, by a prolongation of the latent period before the onset of antibody production, by a delay in the switchover from mercaptoethanol-sensitive (MES) to mercaptoethanol-resistant (MER) antibody production, and by a decrease in the peak titers of MES and MER antibody achieved. At low brucellin dose levels, the MES antibody responses were chiefly depressed; at intermediate dose levels, both the MES and MER antibody responses were depressed; at high brucellin dose levels the MER antibody responses alone were depressed. The nature and degree of suppression of antibody production observed in TxIB mice for a given immunizing dose level of brucellin was equivalent to the suppression obtained through the use of 100- to 1000-fold lower immunizing dose levels of brucellin in normal mice.
The IgM and IgA Immune Response to the TNP Determinant Group in BALB/c Mice
Authors: Mauch Peter , Bridges S. H. , Little K. D. , Little J. Russell
Published: December 2022

These studies document certain features of the splenic IgA plaque-forming cell response and the serum IgA antibody content in BALB/c mice following immunization with TNP-BγG. Differences in the magnitude and temporal sequence of the indirect (IgA) and direct (IgM) plaque-forming cell responses have been documented. Following booster immunization, there was a shorter latent period and higher peak level of cells secreting IgA anti-TNP antibodies suggesting an anamnestic response.
Experimental Autoimmune Renal Cortical Tubulointerstitial Disease in Guinea Pigs Lacking the Fourth Component of Complement (C4)
Authors: Rudofsky Ulrich H. , McMaster Philip R. B. , Ma Wai-Sai , Steblay Raymond W. , Pollara Bernard
Published: December 2022

C4d guinea pigs develop experimental autoimmune renal tubulointerstitial disease indistinguishable from the disease observed in guinea pigs with circulating C4. These data demonstrate that an antibody-mediated autoimmune renal disease can occur in the absence of C4. We conclude: 1) complement may, at least in part, play a role in the pathogenesis, 2) complement activation does not occur via the classical sequence in this model, and 3) that activation and tissue injury may be mediated by an alternate complement pathway.
Augmentation of Immunologic Memory in Mice Following Treatment with Oxisuran
Authors: Fox Alfred E. , Freedman Henry H.
Published: December 2022

Reduction of the priming dose of sheep erythrocytes to mice resulted in a diminished primary response and augmentation of priming for a subsequent secondary response in comparison to normally primed animals. Administration of oxisuran did not influence the reduced primary response and further increased, while 6-mercaptopurine (6-MP) suppressed, priming in low dose-primed animals. Further divergence between oxisuran and 6-MP was expressed in terms of alloantibody production in tail skin allografted mice. Although both agents prolonged allograft survival, in animals given primary grafts oxisuran delayed the appearance of spleen cells forming direct alloantibody, presumably 19S, but did not influence their numbers, while 6-MP was suppressive. Oxisuran-treated grafted mice also demonstrated an earlier than normal appearance of indirect (presumably 7S) alloantibody-forming cells and while peak numbers of such cells were seen at about the same interval after grafting in both treated and untreated animals, oxisuran enhanced, while 6-MP depressed, the number of spleen cells producing 7S alloantibody. These differences were even more apparent in animals given secondary allografts. The results demonstrate that prolonged allograft survival is possible in the presence of either enhanced or depressed alloantibody production. Data from the present study lend further support to the concept that oxisuran modifies T cell function, diverting the response away from cell-mediated hypersensitivity toward immunologic memory.
The Production of Proliferation Inhibitory Factor (PIF) by Mouse Spleen Cells in Vitro
Authors: Badger Alison M. , Cooperband Sidney R. , Merluzzi Vincent J.
Published: December 2022

Concanavalin A and phytohemagglutinin stimulate mouse spleen cells to elaborate proliferation inhibitory factor (PIF) into their culture supernatants. As has been previously described for human PIF, murine PIF is cytostatic in the absence of cytotoxicity and is species-specific. Murine spleen cells, incubated with Escherichia coli lipopolysaccharide, undergo DNA synthesis but do not appear to make PIF.
The Role of Lipid in the Induction of Hapten-Specific Delayed Hypersensitivity and Contact Sensitivity
Authors: Dailey Morris O. , Hunter Robert L.
Published: December 2022

Guinea pigs immunized with bovine serum albumin conjugated with dinitrophenol (BSA-DNP), in Freund's complete adjuvant, produce antibody to the DNP and delayed-type hypersensitivity (DTH) to the BSA. We report that immunization with BSA-DNP doubly conjugated with medium chain fatty acids (L-BSA-DNP) stimulates the production of DTH specific for the hapten DNP with minimal antibody to DNP and no detectable immune response to the carrier BSA. The production of hapten-specific DTH reactions was assessed by two methods. First, animals immunized with L-BSA-DNP produced typical contact sensitivity reactions to epidermal challenge with dinitrofluorobenzene. Second, they produced grossly and microscopically typical delayed hypersensitivity reactions to the intradermal injection of DNP conjugated either to BSA or to a non-cross-reacting carrier, hen egg albumin. In further experiments, DNP-specific DTH was produced by animals immunized with BSA-DNP to which lipid groups had been attached by electrostatic rather than covalent bonds. Evidence is discussed which indicates that the production of DTH to haptens and proteins is largely a function of the lipophilic nature of the entire immunogen and is not dependent upon properties of individual antigenic determinants. Autoradiographic studies with 125I-labeled material demonstrated that the lipid-rich antigens are localized in the paracortical area of lymph nodes, in close proximity to the thymus-derived cells which are stimulated in the induction of DTH.
Specificity and Development of Cytotoxic Thymus-Derived Lymphocytes in Lymphocytic Choriomeningitis
Authors: Doherty Peter C. , Zinkernagel Rolf M. , Ramshaw Ian A.
Published: December 2022

Cytotoxic capacity of immune CBA/H spleen cells for monolayers of L cells infected with lymphocytic choriomeningitis (LCM) virus is abrogated by prior incubation with AKR anti-ϑ ascitic fluid and complement, but is unaffected by treatment with anti-mouse-Ig serum and complement. Depletion of splenic macrophages, or addition of normal or activated (from listeria-immune mice) peritoneal macrophages, does not significantly modify the activity of immune spleen cells. Cell-mediated release of 51Cr from LCM-infected targets may thus be attributed to thymus-derived effector lymphocytes (T cells). Such T cells are specific insofar as they do not exhibit cytotoxic activity for monolayers infected with ectromelia virus, which are readily lysed by homologous immune cells. Development of cytotoxic lymphocytes is related to the dose of virus given: injection of high concentrations leads to peak activity on day 5. Maximal cytotoxicity is, however, mediated by spleen cells taken on day 7 from mice immunized with a relatively small dose of virus.
Effect of Acute of Chronic Infection with Lactic Dehydrogenase Virus (LDV) on the Susceptibility of Mice to Plasmacytoma MOPC-315
Authors: Michaelides Maria C. , Schlesinger Sondra
Published: December 2022

The effect of acute and chronic infection with lactic dehydrogenase virus on the susceptibility of BALB/c mice to the plasmacytoma MOPC-315 has been investigated. The results indicate that the time between infection and tumor challenge is critical in determining how the animals respond to the tumor cells. When the interval was short (1 day) they were more susceptible to tumor formation than were control animals; when 1 to 2 months lapsed between infection and the tumor challenge, they were protected from tumor formation. If the time interval was increased to 5 months no difference between virus-infected and control animals was detected. We propose that the different responses to tumor formation can be attributed to suppression of cell-mediated immunity during acute infection and to its enhancement during the early phase of chronic infection.
The Formation of Stable E Rosettes After Neuraminidase Treatment of Either Human Peripheral Blood Lymphocytes or of Sheep Red Blood Cells
Authors: Galili Uri , Schlesinger Michael
Published: December 2022

Human peripheral blood lymphocytes (PBL) form E rosettes with sheep red blood cells (SRBC) which tend to disintegrate upon incubation at 37°C and which can be disrupted easily by shaking. Neuraminidase treatment of either PBL or SRBC was found to increase the proportion of stable rosettes resistant to prolonged incubation at 37°C and to vigorous shaking. The proportion of stable rosettes formed was related to the concentration of neuraminidase used. SRBC had to be exposed to higher concentrations of neuraminidase than PBL for the production of stable rosettes. Incubation of PBL with absorbed rabbit antiserum to human thymus (RAHT) completely prevented the formation of either stable or regular E rosettes. Rabbit antisera to human bone marrow or brain had no such effect. The concentration of RAHT required for the inhibition of rosette formation by neuraminidase-treated SRBC or PBL was higher than that required for the inhibition of rosette formation by untreated cells. It is suggested that neuraminidase does not “unmask” receptor sites on either SRBC or PBL, but rather reduces the electric surface charge of the cells, thereby enabling a more effective interaction between receptors exposed on the membrane of PBL and sites on SRBC.
The Role of Immunoglobulin in the Interaction of Pneumococci and the Properdin Pathway: Evidence for Its Specificity and Lack of Requirement for the Fc Portion of the Molecule
Authors: Winkelstein Jerry A. , Shin Hyun S.
Published: December 2022

In previous studies on the interaction of pneumococci and the heat labile opsonin (HLO) system it was found that C3 was fixed to the surface of the pneumococcus and that this reaction resulted in opsonization of the organism. The activation of C3 was demonstrated to proceed via the properdin pathway and IgG2, isolated from “non-immune” guinea pig serum (GPS), was shown to participate functionally in the C3 activation. The present studies concern the role of IgG2 in the interaction of pneumococci with the properdin pathway.

The functional activity present in the IgG2 globulin fraction of normal GPS is a 7S immunoglobulin. It is completely removed after passage through an immunoabsorbent column of rabbit-anti-GP IgG1 and IgG2 and is concordant with a 7S peak on sucrose density gradient ultracentrifugation. The Fc portion of the IgG2 is not essential for its activity since after pepsin digestion the activity is retained.

The IgG2 possesses some degree of specificity for the pneumococcus since immunospecific GP IgG2-anti-DNP will not function in the interaction of pneumococci and the properdin pathway. However, both pneumococci and Escherichia coli are able to absorb out the functionally active IgG2, indicating that the immunoglobulin binds to some common surface antigen shared by both organisms.
The Abrogation of Macrophage Migration Inhibition by Pretreatment of Immune Exudate Cells with Anti-θ Antibody and Complement
Authors: Clinton Bruce A. , Magoc Terry J. , Aspinall Richard L.
Published: December 2022

The inhibition of murine (A/J) macrophage migration was not observed after the treatment of the immune exudate cell suspension with AKR anti-θ (C3H) antibody. The complement-dependent cytotoxicity of the anti-θ could be absorbed with target A/J thymocytes; the resulting absorbed anti-θ had no effect on macrophage migration inhibition. There was no cytotoxic effect of the anti-θ antibody and complement on IgM and IgG antibody-forming cells as measured by the hemolytic plaque technique.
A Cell Surface Antigenic Determinant Present on Mouse Plasmacytes and Only about Half of Mouse Thymocytes
Authors: Yutoku Masamichi , Grossberg Allan L. , Pressman David
Published: December 2022

A new surface antigenic determinant present on a subpopulation of normal thymus cells of individual mice has been detected with rabbit antiserum obtained by immunization with cells of a mouse IgM-producing plasma cell tumor, MOPC-104E, and purified by in vivo absorption in mice. Cells of MOPC-104E and several other plasma cell tumors as well as a subpopulation of about 50% of normal mouse thymus cells were found to possess this antigen by cytotoxicity test. Although the present antigen is not plasmacyte-specific since it is also detected on thymocytes, it is not present on liver, kidney, or brain cells, as shown by absorption tests. Hence, it is clearly different from another mouse plasma cell antigen, which has been detected by rabbit antisera prepared similarly against the IgA-producing and IgG-producing plasma cell tumors, ADJ-PC-22A and MOPC-21, respectively, and which is common to liver, kidney, and brain.