bluuebunny/crossref_metadata_2025 huggingface dataset:
A Human T-Independent B Lymphocyte Mitogen Extracted from Nocardia Opaca
Authors: Brochier Jean , Bona Constantin , Ciorbaru Rita , Revillard Jean-Pierre , Chedid Louis
Published: December 2022

Nocardia water soluble mitogen (NWSM), a mitogen specific for mouse and rabbit B cells, activates blood, spleen, and tonsil lymphocytes from all the humans tested. Evidence is presented that it acts selectively on human B lymphocytes. B-enriched cells were recovered from anti-Ig-coated Sephadex columns or after elimination of E rosetteforming cells: they were able to incorporate tritiated thymidine when they were cultivated in the presence of NWSM whereas they were not activated by PWM. Conversely T-enriched suspensions did not respond to NWSM although they were able to be stimulated by PHA and PWM. Moreover, the response to NWSM remained unchanged after T cells had been killed by anti-HTLA serum and complement and disappeared after B cells had been killed by anti-HBLMA serum. After stimulation by NWSM, the number of direct plaque-forming cells to HRBC, LPS, and TNP was significantly increased, showing a polyclonal activation of human B lymphocytes. Since no evidence of T cell help for B cell activation has been found, NWSM thus appears to be a T-independent human B lymphocyte mitogen.
The Effector Cells in Human Peripheral Blood Mediating Mitogen-Induced Cellular Cytotoxicity and Antibody-Dependent Cellular Cytotoxicity
Authors: Nelson David L. , Bundy Bonita M. , Pitchon Howard E. , Blaese R. Michael , Strober Warren
Published: December 2022

The identity of the effector cells in human peripheral blood capable of mediating mitogen-induced cellular cytotoxicity (MICC) and antibody-dependent cellular cytotoxicity (ADCC) was investigated utilizing effector cell populations consisting of purified polymorphonuclear leukocytes, macrophages, lymphocytes, and cell surface immunoglobulin (sIg)-negative and sIg-positive lymphocyte subpopulations obtained by Sephadex anti-Fab immunoabsorbent column fractionation techniques. Chicken erythrocytes (CRBC) and Chang liver cells were used as target cells in both cytotoxicity assays. With CRBC targets, MICC was mediated by polymorphonuclear leukocytes, macrophages, sIg-positive lymphocytes (B cells), and sIg-negative lymphocytes. On the contrary, with Chang liver cells as targets, MICC was mediated only by lymphocytes, and effector cells occurred exclusively in sIg-negative lymphocyte subpopulations containing thymus-derived lymphocytes (T cells). Further purification of sIg-negative lymphocyte subpopulations on antigen-antibody coated plastic surfaces yielded a nonadherent T lymphocyte population depleted of Fc receptor-bearing lymphocytes that was capable of mediating MICC against both CRBC and Chang cell targets. With use of CRBC targets, ADCC was mediated by polymorphonuclear leukocytes, macrophages, and sIg-negative lymphocyte subpopulations. However, with Chang cell targets, ADCC was mediated only by lymphocytes, and effector cells were present only in sIg-negative lymphocyte subpopulations. SIg-positive lymphocytes (B cells) and T lymphocytes were not effective in mediating ADCC against either CRBC or Chang cell targets.

These studies demonstrate that the nature of the target cell employed in MICC and ADCC reactions is of critical importance in defining the effector cell(s) capable of mediating cytotoxicity.
Schistoma Mansoni Soluble Egg Antigens: Determination of the Stage and Species Specificity of their Serologic Reactivity by Radioimmunoassay
Authors: Hamburger Joseph , Pelley Ronald P. , Warren Kenneth S.
Published: December 2022

Three highly purified Schistosoma mansoni egg antigens reactive with sera from mice with chronic schistosomiasis mansoni (major serologic antigens—MSA1, MSA2, and MSA3) were utilized in radioimmunoassays for determining their stage and species specificity. Inhibition studies revealed that MSA1 was completely stage specific, since its binding to S. mansoni chronic infection serum (CIS) could not be inhibited either with cercarial or adult worm antigen. MSA2 and MSA3 were specific with regard to adult worm antigen but their binding to CIS was slightly inhibited by cercarial antigen. Immature eggs in comparison with mature eggs contained only negligible amounts of MSA1 whereas MSA2 and MSA3 were present in large quantities. Fluid from eggs hatched in spring water (hatch fluid-HF) contained considerable amounts of MSA1 as well as MSA2 and MSA3. With regard to species specificity, MSA1 essentially did not cross-react with crude soluble egg antigens (SEA) from Schistosoma japonicum and Schistosoma haematobium whereas MSA2 and MSA3 showed partial cross-reactivity. Antibody dilution studies with sera from animals and humans infected with heterologous schistosome species (i.e., S. japonicum and S. haematobium) indirectly confirmed the high degree of species specificity of MSA1.

The degree of serologic specificity of MSA1 as demonstrated in this study parallels that of the sensitizing activity of S. mansoni eggs and SEA for granuloma formation, as demonstrated in previous investigations. This study, therefore, indicates that MSA1 may be a major immunopathologically active egg antigen. In addition, the high degree of species specificity of MSA1 suggests its use in the serodiagnosis of schistosomiasis mansoni.
Isolation and Characterization of Human B Cell Alloantigens
Authors: Billing Ronald J. , Safani Madjid , Peterson Patricia
Published: December 2022

Human B lymphocyte alloantigens were solubilized from malignant spleen cell membranes from lymphoma patients by detergent treatment or papain digestion. Antigenic activity was detected by inhibition of cytotoxicity of rabbit and human anti-B cell antisera. Extracts from one patient (AC) specifically inhibited only B alloantisera of B groups 1 and 3; sera from B groups 4 and 5 were not inhibited. Inhibitory titers were greater than 1:400 against positive sera and less than 1:2 against negative sera. The papain extracts were purified by QAE-A50 Sephadex and Concanavalin A Sepharose 4B chromatography, and preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (PAGE) under nondenaturing conditions. By testing gel slices for antigenic activity the m.w. of the papain-extracted B antigen was 58,000 whereas the detergent-extracted antigen was 65,000. Antigenic activity detected by rabbit and human antisera copurify together, suggesting that these sera were reacting with the same molecules. Immunoprecipitation of sodium deoxycholatesolubilized extracts of a cultured human B lymphoid cell line 8392 with the rabbit anti-B cell antisera revealed two B cell polypeptides of apparent m.w. 27,000 and 35,000 that were not found on the paired T line 8402. It is suggested that these polypeptides might be subunits of the 65,000 dalton native B lymphocyte alloantigen. The polypeptide subunits do not appear to be linked covalently by disulfide bonds.
Hapten Specific IgE Antibody Responses in Mice
Authors: Fox David A. , Chiorazzi Nicholas , Katz David H.
Published: December 2022

The studies presented in this paper were undertaken to determine whether IgE- and IgG-producing murine B lymphocytes could be distinguished by differential resistance to x-irradiation in vivo. Sensitivity or resistance of B lymphocytes to various doses of x-irradiation was monitored by measuring the production by irradiated cells of haptenspecific IgG and IgE antibody. The results indicate that both primed and unprimed IgG B lymphocytes are less radioresistant than corresponding IgE B lymphocytes. Primed IgG B lymphocytes are more radioresistant than unprimed IgG B cells whereas unprimed IgE B lymphocytes are at least as radioresistant as primed IgE B lymphocytes. The relative radioresistance of primed IgE vs IgG B cells was best demonstrated in an adoptive transfer system. Thus, exposure of ASC-primed mice to 300 R 24 hr after transfer into these mice of syngeneic, DNP-KLH-primed spleen cells led to a sustained failure to produce IgG anti-DNP antibody after challenge with DNP-ASC; under these conditions IgE anti-DNP production was not impaired. This was shown to reflect differential radioresistance of the corresponding B cell populations. In addition, exposure to x-irradiation tended to augment IgE anti-DNP antibody responses when compared to unirradiated controls. This phenomenon is thought to reflect the effects of x-irradiation on regulatory mechanisms controlling the mouse IgE response and is explored in detail in an accompanying manuscript. The results described in this paper are discussed in the light of our evidence suggesting that, in both mouse and man, IgE B lymphocytes have certain unique characteristics by which they may be distinguished from other classes of B lymphocytes.
Hapten-Specific IgE Antibody Responses in Mice
Authors: Chiorazzi Nicholas , Fox David A. , Katz David H.
Published: December 2022

Exposure of BALB/c, A/J, and (BALB/c × A/J)F1 mice, which are IgE high responder animals, to total body x-irradiation ranging from 50 to 200 R resulted in a dose-dependent enhancement of the hapten-specific IgE antibody level as compared to unirradiated control mice. In contrast, anti-hapten antibody responses of the IgG class in these same animals were rarely enhanced, and when so, were of a lesser degree. This relatively selective augmentation of the IgE vs IgG antibody responses was observed in both unprimed and primed mice. By utilizing adoptive transfer systems, it was demonstrated that the enhancing effects of x-irradiation resulted from its action on the carrier-primed cell population and not upon the responding B cells or upon macrophages. The data presented herein suggest that this enhancement phenomenon is the result of the elimination of T cells (or their products) with suppressive functions and that these cells are neither dependent upon nor specific for the carrier antigen employed in the immunization. This hypothesis is given indirect support by the observations that treatment of the same strains of mice with cyclophosphamide, in doses known to abrogate suppressive T cell functions, resulted in a similar enhancing effect to that observed after low doses of x-irradiation.

In addition an interesting difference between IgE and IgG precursor B lymphocytes was observed by the ability of IgE B cells to differentiate to the secretory state at a strikingly more rapid rate than IgG B lymphocytes when exposed to comparable T cell helper influences. These observations may provide important clues to the cellular mechanisms of the immune regulation of the IgE response and its relationship to allergic diseases.
The Inhibition of Initial Steps of Lymphocyte Transformation by Cytochalasin B
Authors: Resch Klaus , Prester Marlot , Ferber Ernst , Gelfand Erwin W.
Published: December 2022

CB was shown to inhibit the PHA-induced activation of rabbit lymph node lymphocytes as assessed by the incorporation of 3H-uridine into RNA or 3H-thymidine into DNA. This suppression was dose dependent with an optimum of 10 µg CB/ml (20. 8 µM). Mitogen-activated lymphocytes escaped the inhibitory effect of the drug when CB was added later than 1 hr after the addition of PHA. CB also suppressed the activation of membrane phospholipid metabolism which occurs among the earliest detectable changes in activated lymphocytes. Thus the incorporation of 14C-choline, 14C-acetate, or 14C-oleate into lecithin in the presence of PHA and CB was the same as the level of their incorporation in unstimulated lymphocytes. The increased incorporaion of 14C-oleate into lecithin of the plasma membrane of activated lymphocytes was similarly prevented in the presence of CB. In contrast, CB exhibited no or only a marginal effect on the phospholipid turnover of unstimulated lymphocytes. Our results point to plasma membrane phospholipid metabolism as the possible site of CB interference with the lymphocyte activation.
Characterization of Macrophage Migration Inhibitory Factor Activity Produced in Vivo by a Cell-Mediated Immune Reaction in the Guinea Pig
Authors: Postlethwaite Arnold E. , Townes Alexander S. , Kang Andrew H.
Published: December 2022

Peritoneal fluid from the abdominal cavities of guinea pigs having delayed hypersensitivity to horseradish peroxidase (HRPO) was obtained by a lavage technique before and after i.p. challenge with antigen. Macrophage migration inhibitory factor (MIF) and macrophage chemotactic factor activities were measured in peritoneal fluids from each animal. Chemotactic activity for macrophages was maximal 24 hr after i.p. challenge and was absent thereafter. MIF activity was maximal in peritoneal fluid 24 to 48 hr after challenge. Macrophages were present in greatest numbers in peritoneal fluid 24 hr after challenge and returned almost to control levels at 48 hr. Macrophages in 48-hr fluid were larger and exhibited more intense cytoplasmic staining for nonspecific esterases when compared to those in 0-hr fluid.

The m.w. of MIF obtained from culture supernatants of HRPO-stimulated guinea pig lymphocytes and 48-hr peritoneal fluid were found to be virtually identical, 58,000 and 54,000 daltons, respectively. MIF from these in vitro and in vivo sources were similarly resistant to heating at 56°C for 30 min but were both destroyed by incubation with insoluble trypsin.
Binding of IgE Myeloma Proteins to Human Cultured Lymphoblastoid Cells
Authors: Gonzalez-Molina Andres , Spiegelberg Hans L.
Published: December 2022

The binding of human IgE myeloma proteins to 16 human cultured lymphoblastoid cell lines was studied by measuring specific uptake of radiolabeled deaggregated IgE myeloma proteins and/or E-IgE rosette formation. Eight lines, RPMI-8866, Wil-2WT, RPMI-6410, RPMI-1788, RPMI-4265, Clowers, COLO-59 and Victor, bound IgE as shown by at least one of these methods. The lines, RPMI-4098, SCRF-5004, NC-37, Daudi, Raji, P3JHR-1, RPMI-1301 and Molt-4 did not bind IgE. Of the positive cell lines, 58 to 98% of the cells formed E-IgE rosettes. The binding of IgE was Fc fragment specific. It could only be inhibited by human IgE and its Fc fragment but not by IgE Fab fragments and Ig of other classes. The binding of IgE also appeared to be species specific, since a rat IgE myeloma protein did neither bind to the cells nor inhibit the binding of human IgE. The binding of IgE was relatively temperature independent and was abolished by trypsin and pronase pretreatment of the cells. Most of the cell lines binding IgE did not bind IgG but had surface immunoglobulin and did not form spontaneous E rosettes. These data suggest that certain lymphoblastoid cells may have receptors for IgE.
Purification and Partial Characterization of a Tumor-Specific Blocking Factor from Sera of Mice with Growing Chemically Induced Sarcomas
Authors: Nepom Jerry T. , Hellström Ingegerd , Erik Hellström Karl
Published: December 2022

The purification of a blocking factor from the sera of tumor-bearing mice is described. Whole serum with blocking activity—the ability to inhibit specific cell-mediated anti-tumor immunity in microcytotoxicity tests—was fractionated on immunoadsorbent columns containing Sepharose-bound syngeneic normal mouse immunoglobulins and immunoglobulins from tumor-immune donors. The blocking serum was derived from mice which had carried a transplanted methylocholanthrene-induced sarcoma for 21 to 28 days. Elution of the immunoadsorbents recovered the blocking activity in a single fraction. This fraction was radiolabeled and analyzed by SDS gel electrophoresis and Sephadex G-200 column chromatography. The active component of the blocking serum was shown to be a polypeptide of m.w. 56,000.

Specificity testing implied that the factor was likely to be either tumor antigen or an antigen-specific suppressor molecule.
Cell Interactions Between Histoincompatible T and B Lymphocytes
Authors: Katz David H. , Chiorazzi Nicholas , McDonald Jeanne , Katz Lee R.
Published: December 2022

Two possible explanations for the failure of primed histoincompatible T and B lymphocytes to cooperate in secondary responses of the IgG antibody class have been investigated in the present study: 1) The possible existence of subtle suppressive mechanisms developing as a consequence of mixing two histoincompatible cell populations; and 2) The possible inability of histoincompatible carrierprimed T cells to recognize and/or be induced to function by carrier determinants presented to them in association with foreign MHC antigens (i.e., the “altered-self” recognition hypothesis). Absence of suppression has been verified by two different approaches, including: 1) the failure of histoincompatible T cells, even in great excess, to interfere with physiologic cooperation between syngeneic T and B lymphocytes; and 2) the failure of histoincompatible B cells to interfere with physiologic cooperation between semi-syngeneic F1 hybrid T cells and parental B cells. The unlikelihood of the “altered-self” explanation for failure of histoincompatible T and B cells to cooperate has been indicated by an inability to circumvent the requirement for I-region identity by priming T cells with allogeneic macrophagebound antigen even when the latter cells are of identical haploytpe with the allogeneic B cells employed in the final cooperation assay.

These results strongly substantiate the existence of true genetic restrictions in T-B cell intractions in secondary responses to hapten-protein conjugates. The validity of other observations indicating an absence of genetic restrictions in certain circumstances, considered in the context of our own data, has suggested the possibility that virgin T and B lymphocytes reciprocally influence one another during the course of cell interactions in response to antigenic and/or other signals, a process we term “adaptive differentiation.”
Activation of the Alternative Pathway of the Complement System by Radiographic Contrast Media
Authors: Arroyave Carlos M. , Naras Bhat K. , Crown Ronald
Published: December 2022

Nine patients who underwent radiographic contrast media (RCM) infusion for diagnostic purposes were studied. Simultaneously, venous blood samples were collected and complement was measured. None of the patients had a clinical history of allergy to previous infusion of RCM. A significant drop in plasma complement (CH50) levels was detected in five of nine patients. The drop in CH50 was observed wihin the first 20 min after the initiation of RCM infusion. All five patients in whom a drop in complement was found showed a decrease in hemolytic C3, properdin, and factor B. In addition, by radial immunodiffusion low levels of C3, C6, properdin, and factor B were observed and split products of C3 and factor B were identified by immunoelectrophoresis. No significant changes in C1q and C4 were detected by radial immunodiffusion during the study of these five patients. This study strongly suggested that in some patients undergoing RCM infusion, activation of the complement system occurred and this activation appears to be through the alternative pathway.
Electrophoretic Separation of Radioisotopically Labeled Mouse Lymphocytes
Authors: Griffith A. L. , Catsimpoolas N. , Dewanjee M. K. , Wortis H. H.
Published: December 2022

A new preparative method is described for the separation and direct electrophoretic comparison of the distribution profile of radioisotopically labeled cells. The cell populations to be compared are labeled separately with different radioisotopes (e.g., 51Cr and 99mTc) and mixed. The cell mixture is subjected to density gradient electrophoresis and the distribution of each radioisotope in the collected fractions is ascertained by differential gamma counting. In the case of uniform label uptake by the cells in each distribution, the radioactivity counts represent cell frequency. Nonuniform labeling allows useful comparisons only in terms of relative mobility distribution. Model experiments performed with 51Cr- and 99mTc-labeled mouse thymocytes and spleen cells are in general agreement with mobility distribution results obtained previously by free flow electrophoresis.
Immunity to Phasmodium Berghei Yoelii in Mice
Authors: Weinbaum Fredric I. , Evans Charles B. , Tigelaar Robert E.
Published: December 2022

The course of infection with 17X nonlethal Plasmodium berghei yoelii was examined in BALB/c mice which were deficient in either T cells or B cells. Markedly increased parasitemia and mortality were observed in athymic (nude) mice which had been backcrossed on a BALB/c background (T cell deficient) compared to similar mice which had been grafted with neonatal BALB/c thymus, and were also observed in BALB/c mice suppressed from birth with goat antiserum to mouse µ-chain (B cell deficient) compared to age- and sex-matched BALB/c controls. These results establish the requirement for the presence of both T cells and B cells for effective resistance to an intercurrent infection with 17XNL P.b. yoelii in adult BALB/c mice. Mechanisms by which the requirement for both T cells and B cells could be explained were discussed. The model of µ suppression was shown to be a valuable tool for an evaluation of the cellular basis of immunity to an infectious disease.
Triggering of Human Peripheral Blood B Cells: Polyclonal Induction and Modulation of an in Vitro PFC Response
Authors: Friedman Steven M. , Breard Jacqueline M. , Chess Leonard
Published: December 2022

In the present studies we utilized polyclonal activators to analyze the signals required to induce antibody synthesis by subpopulations of human peripheral blood lymphocytes. The in vitro synthesis of antibody directed against sheep erythrocytes was measured by a modification of the Jerne plaque assay. The plaques observed contained central lymphoid cells, could be inhibited by anti-human immunoglobulin, and were strictly dependent on both the addition of complement and viable B lymphocytes actively synthesizing protein. Kinetic analysis showed that the PFC response developed over time during cell culture with peak activity occurring between days 6 and 7.

It was found that human peripheral blood B lymphocytes, isolated by Sepahdex G-200 anti-Fab column chromatography, were nonspecifically induced by either PWM or soluble products of antigen-activated human T cells to differentiate into PFC. In contrast, unfractionated peripheral blood lymphocytes, Ig- cells isolated from immunoabsorbant columns, and B cells enriched by nylon wool adherence were not triggered to antibody synthesis even in the presence of polyclonal activators. B cells isolated by nylon wool adherence and further fractionated by binding and elution from anti-Fab columns were then readily triggered by PWM to differentiate into PFC. These results suggest that the interaction of human B cells with anti-Fab columns, presumably at the Ig receptor, serves as a signal important in the differentiation events leading to PFC activity. The anti-Fab interaction alone, although critical, was not sufficient to induce the differentiation of precursor cells into PFC since subsequent triggering by antigen-activated T cell supernatants or PWM was required for the development of an optimal PFC response.

Additional experimental data demonstrated that the PFC response could be regulated by autologous peripheral Ig- lymphoid cells in vitro. At low concentrations of PWM, Ig- cells consistently augmented the B cell PFC response whereas at high concentrations of PWM, suppression was observed. Depletion of E rosetting cells from the Ig- population eliminated the subset responsible for augmentation but did not eliminate the suppressor cell activity.
Genetic Control of Immune Responsiveness to Poly (lPro)—Poly (lLys)-Derived Polypeptides by Histocompatibility-Linked Immune Response Genes in the Rat
Authors: Günther Eberhard , Mozes Edna , Rüde Erwin , Sela Michael
Published: December 2022

In rats responsiveness to branched synthetic polypeptides carrying a Pro—L backbone, such as (T,G)-Pro—L or (Phe,G)-Pro—L and to Pro—L itself is controlled by Ir genes which are linked to the major histocompatibility genes. The level of antibody production to these polypeptides does not fall into strict high or low responder categories but covers the range in between. (T,G)-Pro—L and Pro—L elicit a very similar response pattern which, however, differs from that obtained with (Phe,G)-Pro—L. Anti-(T,G)-Pro—L antibodies do not cross-react with (T,G)-A—L, but do so extensively with Pro—L. Anti-(Phe,G)-Pro—L antibodies show cross-reactivity to (Phe,G)-A—L only when the antibody-producing strain is a high responder to (Phe,G)-A—L. These results when considered in view of data obtained in mice on genetic control of the immune response to (T,G)-Pro—L suggest that at least two unlinked Ir genes are involved in controlling anti-Pro—L responsiveness.
The Regulation of the Immune Response to T-Independent Antigens by Prostaglandins and B Cells
Authors: Zimecki Michal , Webb David R.
Published: December 2022

The effect of inhibitors of prostaglandin synthesis on the in vitro primary immune response to two T-independent antigens has been investigated. The results, with PVP or DNP-Ficoll, suggest that the prostaglandins play an important role in the regulation of the immune response to these antigens. Furthermore, it appears that B cells may be involved in their own regulation by synthesizing and responding to prostaglandins. Although it has been previously established that T cells exert a regulatory influence on the response to PVP and DNP-Ficoll, this is the first demonstration of an apparent B cell regulation of B cell function via the production of a specific hormone.
Tuberculin-Sensitized Lymphocytes Detected by Altered Electrophoretic Mobility Distributions after Incubation with the Antigen PPD
Authors: Uzgiris E. E. , Kaplan Joel H.
Published: December 2022

Lymphocytes from donors who had had tuberculosis (a disease known to provoke a cell-mediated immunity) were incubated with the tuberculin antigen, purified protein derivative (PPD), and their distribution of electrophoretic mobility was determined by laser Doppler spectroscopy. In 75% of the cases, the distribution showed a new, high mobility cell subpopulation that was not present before exposure to the PPD. Control lymphocytes from individuals with negative skin tests or no record of tuberculosis showed no mobility changes after incubation with PPD. These observations indicate that the new mobility subpopulation arose from a specific interaction between the antigen and sensitized cells of the donors.
The Development of HBsAg-Positive Hepatitis Despite the Previous Existence of Antibody to HBsAg
Authors: Koziol Deloris E. , Alter Harvey J. , Kirchner John P. , Holland Paul V.
Published: December 2022

A dentist developed acute, icteric HBsAg-positive hepatitis despite the prior existence of anti-HBs. Evaluation of this antibody showed it to have a restricted specificity reacting with only one subdeterminant (α1) of the hepatitis B surface antigen. The anti-HBs/α1 coexisted with HBsAg of subtype ayw in the acute phase hepatitis serum.
Specificity of the in Vitro Immune Response to Synthetic Polypeptide Antigens in Inbred Rats
Authors: Minford Jon K. , Cramer Donald V. , Gill Thomas J.
Published: December 2022

The immune response to a variety of synthetic and natural antigens is under the control of genes present within the major histocompatibility complex (MHC), and many of the responses are mediated by thymus-derived lymphocytes (1–3). These immune response (Ir) genes may code for cell-surface structures that are capable of specific antigen recognition, either by direct interaction with the antigen or by conformational changes in association with other cell surface structures (1, 2).

The specificity of the proposed Ir gene product on the T cell has been examined by comparing the cross-reactivities of antibodies and of sensitized cells elicited by immunization with branched synthetic polypeptide antigens. McDevitt and his co-workers have presented evidence that the in vitro recognition of antigen by T cells in the mouse is more specific than either antibody cross-reactivity or antigen binding by B cells (4, 5). Similar results were obtained in the rat by comparing the cross-reactions of anti-polypeptide antibodies and the in vitro antigen-induced proliferative response (6).
Letters to the Editor
Authors: Silverman Morton S. , La Via Mariano F.
Published: December 2022

Dear Sir: We wish to alert our colleagues to a possible hazard in using phenol containing disinfecting agents in laboratory animal facilities.

For several years, we have used CBA male mice and routinely perform Mishell-Dutton-type cultures of mouse spleen cells immunized with sheep erythrocytes (SRBC). Our normal anti-SRBC response is around 300 to 500 PFC with a background of around 30 to 40 PFC/106 recovered cells. In November 1975, we inadvertently started using O-Syl (National Laboratories, Lehn & Fink Industrial Products Division of Sterling Drug, Inc., Montvale, N. J. 07645) to disinfect the polypropylene cages in which mice are housed (10 to 15/cage). Cages were disinfected weekly by a mixture of hot water and O-Syl (approximately 10 ml in 10 liters of hot water) and rinsed repeatedly with warm water. By February 1976, the anti-SRBC response in spleen cultures declined to around 60 PFC/106 recovered cells. Shortly thereafter the mice developed a dermatitis.
Effect of Sensitization with Propionibacterium Acnes on the Growth of Listeria Monocytogenes and Treponema Pallidum in Rabbits
Authors: Baughn Robert E. , Musher Daniel M. , Knox John M.
Published: December 2022

Sensitization of rabbits with Propionibacterium acnes, a nonspecific stimulant of the reticuloendothelial system, was investigated as a means of enhancing resistance to Treponema pallidum. A single i.v. dose of P. acnes given 3 or 7 days before challenge with Listeria monocytogenes was capable of suppressing the growth of the heterologous organism, whereas a single i.v. dose 24 hr or 14 days before challenge was not. Reactivation via i.v. elicitation with P. acnes 14 days after sensitization (1 day before challenge) caused significant suppression of listerial growth in the major organs 30 hr after i.v. challenge. A series of similar experiments was designed with T. pallidum as the challenge organism. Sensitization and repetitive elicitation with P. acnes did not change the time of appearance or progression of syphilitic chancres after i.v. or i.d. challenge. Injection of P. acnes into sites of intradermal T. pallidum challenge in previously sensitized rabbits also failed to alter the evolution of syphilitic lesions. These results suggest that macrophage activation does not alter the host's ability to suppress the growth of T. pallidum.
Immune Interactions with Cells Infected with Herpes Simplex Virus: Antibodies to Radioiodinated Surface Antigens
Authors: Glorioso Joseph C. , Smith Jerry W.
Published: December 2022

Lactoperoxidase-catalyzed radioiodination was used to study reactions between surface antigens and antibodies on BHK-21 cells infected with HSV-1 and HSV-2. Isolation of iodinated surface antigens was achieved by indirect immune precipitation of Triton X-100-disrupted cells with antisera to HSV and IgG. Analysis of immune precipitates by polyacrylamide gel electrophoresis (PAGE) revealed at least 10 antigens, ranging in m.w. from 35 × 103 to 160 × 103 daltons. Antigens were detectable on cell surfaces as early as 2 hr post-infection. Electrophoretic patterns of surface antigens induced by HSV-1 were similar to those induced by HSV-2. In both cases the major portion of activity was associated with glycoprotein(s) in the range of 115 × 103 to 130 × 103 daltons. A reduced amount of radioactivity was obtained if cells were reacted with anti-HSV sera before disruption with Triton X-100, suggesting that less surface antigen was accessible to HSV antibody applied directly to intact cells.
Histamine Modulation of Eosinophil Migration
Authors: Clark Richard A. F. , Sandler Jeffrey A. , Gallin J. I. , Kaplan Allen P.
Published: December 2022

Preincubation of eosinophils with 10-5 M or higher concentrations of histamine inhibited the eosinophil chemotactic response to endotoxin-activated serum whether by using the nucleopore filter assay and counting the cells migrating through the filter, or by using the Zigmond-Hirsch assay and counting the cells at each 10-µm interval. When the H2-receptor sites on the eosinophils were blocked by metiamide, the inhibitory capacity of histamine was prevented. Preincubation of eosinophils with 10-6 M histamine increased the number of responding eosinophils to endotoxin-activated serum and this enhancement was blocked by an H1-receptor antagonist.

Isoproteronol and aminophylline inhibited eosinophil movement and increasing concentrations of dibutryl cyclic AMP inhibited eosinophil migration. Concentrations of histamine that consistently resulted in inhibition of eosinophil movement stimulated an increase in cyclic AMP that was prevented by blocking the H2-receptor but not the H1-receptor. Thus, histamine-dependent inhibition of the eosinophil chemotactic response to other agents is mediated through the H2-receptor and is associated with an increase in the intracellular level of cyclic AMP whereas histamine dependent enhancement of eosinophil migration to other agents appears to be mediated through the H1-receptor.

Eosinophils behave as a heterogeneous population as assessed by the ability of histamine to augment or inhibit cell migration. This may reflect differences in H1 to H2 receptor density or cell responsiveness to receptor stimulation. The chemoattractant activity of histamine itself is not influenced by H1 or H2 receptor antagonists, thus it is possible that an eosinophil has a third type of histamine receptor.
Requirement for Non T-Cells in the Generation of Cytotoxic T Lymphocytes (CTL) in Vitro
Authors: Miller Richard G. , Schilling Rainer M. , Phillips Robert A.
Published: December 2022

Small numbers of LN cells will produce many more cytotoxic lymphocytes on in vitro culture with allogeneic stimulator cells if spleen cells from nu/nu mice are also present throughout the culture period. All cytotoxic cells produced are T cells and arise from precursors in the LN component. The nude spleen component appears to be providing a required non-T cell which has been lost from the LN component through dilution. At least two active subpopulations of cells, differing in sedimentation velocity, adherence properties, radiation sensitivity, and antigen recognition properties can be identified in the nu/nu spleen. The first, the dominant activity in normal nu/nu spleen, is nonadherent, radiation sensitive, and can synergize with either syngeneic or allogeneic LN cells provided both are different from the same alloantigens in the stimulator population. The second, found in nu/nu spleen cells precultured with alloantigen, sediments more rapidly, is adherent, and radiation resistant, and need not be allogeneic to the stimulator cells to synergize with LN cells. The first subpopulation may give rise to the second.
Anti-Thymocyte Autoimmunity in BALB/c Mice Accompanying Immunization to a Syngeneic Lymphoma
Authors: Baechtel F. Samuel , Prager Morton D.
Published: December 2022

As immunization of BALB/c mice to the syngeneic P1798 lymphoma is effected by administration of iodoacetamide-modified P1798 cells, serum antibodies appear which are reactive with P1798 and normal BALB/c thymocytes, splenocytes, and peripheral blood lymphocytes. Anti-P1798 serum also cross-reacted with thymocytes from AKR, DBA/2, and C3H mice as well as the allogeneic lymphoma 6C3HED. Anti-P1798 serum was unreactive with the Thy-1 deficient L1210 lymphoma. Multiple absorptions of anti-P1798 serum with normal BALB/c thymocytes or brain or P1798 removed antibodies to P1798 and thymocytes commensurately. Normal BALB/c liver and kidney did not absorb antibody activity. Treatment of a BALB/c splenocyte suspension with anti-Thy 1.2 serum and complement removed the population of spleen cells which were capable of reaction with anti-P1798 serum. The data suggest that antibodies to P1798 and thymocytes are the same and that specificity may be directed toward a Thy-1 related structure but without distinguishing Thy-1.1 and Thy-1.2.
Mitogenic Responsiveness and Monocyte-Lymphocyte Interaction of Early and Late Rosette-Forming Cell Populations of Human Peripheral Blood Lymphocytes
Authors: Taniguchi Noboru , Miyawaki Toshio , Moriya Naoki , Nagaoki Takeshi , Kato Eiji , Okuda Norihiko
Published: December 2022

Adherent cells in human peripheral blood mononuclear cells were removed by the attachment to the plastic surface of tissue culture dishes. After removal of adherent cells, early rosette-forming cells (early RFC), which were characterized by early (5 min) rosette formation with sheep blood cells (SRBC) at an SRBC to lymphocyte ratio of 8:1, were separated from nonrosetting cells by sedimentation on Ficoll-Hypaque gradient. Total (60 min) rosette formation was carried out with the early RFC-depleted cell population on the gradient interface by the use of neuraminidase-treated SRBC at an SRBC to lymphocyte ratio of 20:1 and the resulting rosette-forming cells (late RFC) were sedimented by gradient centrifugation. These T cell subpopulations, early RFC-enriched and late RFC-enriched, were reasonably pure with respect to the ability to bind SRBC and contained less than 0.5% monocytes. Monocyte preparations, which were obtained after vigorous washing of the adherent cell layers on tissue culture dishes, responded to phytohemagglutinin P (PHA-P) or concanavalin A (Con A) with negligible incorporation of 3H-thymidine.

There was no significant difference in the responsiveness to PHA-P between early RFC-enriched and late RFC-enriched populations either in the absence or in the presence of graded numbers of additional autologous monocytes. However, the response of early RFC-enriched population to Con A was significantly poor as compared with that of late RFC-enriched one unless additional monocytes were added. In the presence of 20% autologous monocytes in the culture, the Con A-induced response of early RFC-enriched population was markedly enhanced to reach close to that of late RFC-enriched population. These results suggest that early RFC and late RFC might be different from each other in their responsiveness and in their need for monocytes on the stimulation with Con A.
Immune Response to Acute Otitis Media in Children
Authors: Sloyer John L. , Howie Virgil M. , Ploussard John H. , Bradac James , Habercorn Marilynn , Ogra Pearay L.
Published: December 2022

With the technique of radioimmunodiffusion and indirect FA staining, IgA antibody to measles, mumps, rubella, and polio-1 were determined in serum and middle ear fluid (MEF) of 103 patients with otitis media. The occurrence of IgA viral antibody in MEF and its absence in simultaneously drawn serum was used as an indicator of local antibody production. Of the 401 assays performed, 41 instances of IgA antibody exclusively in MEF were found. Only four of these occurred in specimens from unimmunized patients and were directed against rubella virus. Of the 37 remaining cases, 16 each were directed against measles and polio-1 and four and one, respectively, for mumps and rubella viruses. The mean specific IgA titers were from 8- to 17-fold higher in MEF from immunized individuals than in the unimmunized and persisted for at least 9 to 19 months after immunization. The data thus indicate 1) specific immunologic sensitization of the middle ear mucosa can be achieved by parenteral as well as oral routes of immunization, and 2) specific immunologic memory exists in the middle ear mucosa. These two factors are crucial to feasibility of immunization against acute otitis media.
Immunologic Injury in Measles Virus Infection
Authors: Perrin Luc H. , Tishon Antoinette , Oldstone Michael B. A.
Published: December 2022

Human peripheral blood leukocytes (PBL) from patients with chronic measles virus infection (SSPE) or from immune, adult humans (convalescent from acute childhood measles virus infection) are cytotoxic for target cells infected with measles virus as measured by a 51Cr assay. Specific release of 51Cr by immune PBL occurred both with and without human antibodies added to measles virus-infected cultures. Maximal killing in the absence of added antibodies to measles virus was usually detected only after 15 to 18 hr of incubation and with a high PBL to target ratio (100:1). When antibody to measles virus was added, PBL-mediated killing of virus-infected cells was not blocked. Instead, killing was enhanced and maximal lysis occurred with fewer PBL and a shorter incubation time. This cytotoxic reaction was inhibited in a dose-response manner upon the addition of Fab fragments of IgG containing antibodies to measles virus. On the average 4 to 5 × 105 antibody molecules bound per infected target cell before initiation of antibody-enhanced PBL killing.

Depletion of either glass-adhering or E-rosette-forming cells did not reduce PBL killing of measles virus-infected target cells in either system. In contrast, removal of non-E rosette or of EAC rosette-forming population of PBL almost completely abrogated cytotoxicity. When Fc-bearing cells were removed, killing of virus-infected target cells was concomitantly reduced. Lysis of measles virus-infected target cells did not require histocompatibility between the PBL and the target cell. Further, immunospecific lymphocyte killing was not enhanced by such a histocompatibility fit. These experiments indicate first, that the effector PBL involved in lysis of measles virus-infected targets are not T cells but are probably K cells and, second, that PBL obtained from patients with SSPE are competent in killing measles virus-infected targets. Moreover, sera from SSPE patients did not contain a factor(s) that blocked PBL-mediated cytotoxicity.
Host Cell Modification of Lymphocytic Choriomeningitis Virus and Newcastle Disease Virus Altering Viral Inactivation by Human Complement
Authors: Welsh Raymond M.
Published: December 2022

Complement in human serum inactivated several enveloped viruses, but for some viruses the degree of inactivation depended on their passage history. In short, human serum detected cell-induced modifications of virions. Normal human serum, lacking detectable neutralizing antibodies to the virions, inactivated lymphocytic choriomeningitis virus (LCMV) and Newcastle disease virus (NDV) when the viruses were passed through some cell lines but not others. Host cell modification was further documented with LCMV since antibody to the cell (in conjunction with a complement source) inactivated virus produced by that cell. The mechanism by which human serum inactivated LCMV passed through L cells was determined. By using serum immunochemically depleted in the classical complement pathway component C4 and/or the alternative complement pathway component factor B, as well as other methods, it was shown that LCMV was inactivated via the classical complement pathway. Absorption and immune precipitation experiments indicated that the inactivation of LCMV by complement was mediated by natural antibody directed against the host (L-929) cell. NDV grown in chick embryo cells could be inactivated by either complement pathway in the absence of the other. A requirement for antibody could not be demonstrated in the NDV system. On the basis of these data it is proposed that alterations in virulence dependent upon passage of the virus in cells or animals may be partially explained by changes in virus sensitivity to human serum inactivation.
Activation of the Classical and Properdin Pathways of Complement by Bacterial Lipopolysaccharides (LPS)
Authors: Morrison David C. , Kline Lois F.
Published: December 2022

Bacterial lipopolysaccharides (LPS) have been demonstrated to activate both the classical and the properdin pathways of complement. The lipid A region of the LPS is responsible for classical pathway activation and the polysaccharide region responsible for properdin pathway activation. Classical pathway activation by lipid A does not depend upon antibody to the lipid A and properdin pathway activation proceeds by a lipid A-independent mechanism. The polysaccharide portion of the LPS molecule exerts a modifying influence on the potential anticomplementary activity of the lipid A.
Immunization with p30 Enhances the Growth of a Rat Moloney Sarcoma
Authors: Jones Joe M. , Kennel Stephen J. , Feldman Joseph D.
Published: December 2022

p30, a core polypeptide, and gp 70, an envelope glycoprotein of C-type RNA tumor viruses, are present on the surface membranes of tumors induced by C-type virus. They have also been implicated in the development of host immunologic resistance to tumor growth (1–5). We have immunized rats with homogeneous preparations of p30, gp 70, and intact tumor cells to study their role in the growth and progression of challenge with a rat Moloney sarcoma (MST).3 MST produces Moloney leukemia virus (MuLV) particles in vitro and in vivo (6).

Cultures of rat Moloney sarcoma cells (MST) were prepared from tumors induced by injecting MSV extracted from tumors of BALB/c mice into newborn Brown Norway (BN) rats (6). Cultures of cells were also prepared from a sarcoma induced by injecting newborn BN rats with 3-methylcholanthrene (BC5). BC5 cells were free of virus by electron microscopic and antigenic analyses (see below).
Complement Activation by Interaction of Polyanions and Polycations
Authors: Claus D. R. , Siegel J. , Petras K. , Skor D. , Osmand A. P. , Gewurz H.
Published: December 2022

Interactions between heparin and protamine previously were found to result in activation of the complement (C) system. In the present investigation, this interaction was shown to result in the binding of purified C1̄, and this was markedly enhanced in the presence of C-reactive protein (CRP). CRP also enhanced C consumption during heparin-protamine interactions in whole serum, and in the presence of CRP depletion of C components C1-3 was observed. Similar C1 binding and C consumption in the presence of CRP were seen upon the interaction of multiple additional polyanions including DNA, ENA, hyaluronic acid, chondroitin sulfate, and dextran sulfate with the polycations protamine sulfate and poly-L-lysine. These effects were observed with CRP concentrations well within the range found in normal human sera and considerably less than those found in most acute phase sera. We suggest, therefore, C activation by polyanion-polycation interactions in the presence of CRP may be important to certain reactions of host defense and inflammation.
T and B Lymphocyte Migration into Syngeneic Tumors
Authors: Elboim Charles M. , Reinisch Carol L. , Schlossman Stuart F.
Published: December 2022

The migration of splenic T and B lymphocytes into syngeneic tumors undergoing immunologic rejection was investigated. Spleen cells were obtained from normal BALC/c mice or BALB/c mice bearing tumors induced by murine sarcoma virus (MSV). Either whole spleen cells or immunoabsorbent purified T and B cells were radiolabeled with sodium chromate-51 and injected i.v. into normal or MSV induced-tumor bearing syngeneic recipients. Twenty-four hours later the recipient mice were sacrificed and radioactivity was assessed for tumor, contralateral normal muscle, the lymph nodes draining the tumor and contralateral draining lymph nodes, peripheral lymph nodes, spleen, and liver.

Both T and B lymphocytes from either normal or MSV tumor-bearing animals show greatly increased migration into the tumor when compared with normal muscle. Migration of T cells from both normal and MSV tumor bearers was 30 times that of migration to normal muscle. B cells from tumor-bearing mice, on the other hand, localized in the tumor itself only 50% as frequently as did B cells from normal animals. In addition, T cells from MSV tumor bearers were found in the highest proportion in the lymph node draining the tumor site.

We conclude that T and B lymphocytes from either normal or tumor-bearing mice migrate to a syngeneic tumor undergoing immunologic rejection. In contrast, the migration of both T and B cells from tumor-bearing animals was decreased to the peripheral lymph nodes at the time of maximum tumor growth.