bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autoimmune Response to DNA, Red Blood Cells, and Thymocyte Antigens in Association with Polyclonal Antibody Synthesis During Experimental African Trypanosomiasis
Authors: Kobayakawa Takatoshi , Louis Jacques , Izui Shozo , Lambert Paul-Henri 
Published: January 2023

Abstract
In vivo induction of autoantibodies by polyclonal B cell activators has been suggested to be the direct consequence of the polyclonal B lymphocyte activation. Since the appearance of various autoantibodies represents a common feature of some parasitic infections, the possibility that such autoantibodies develop as a result of the stimulation of polyclonal antibody synthesis was tested in mice infected experimentally with Trypanosoma brucei brucei (T. brucei).
Polyclonal antibody production in the spleen was measured by the Cunningham plaque-forming cell (PFC) assay with SRBC, TNP-SRBC, and FITC-SRBC as indicator cells. Compared with normal mice, T. brucei-infected animals displayed a marked increase in the number of PFC to TNP, FITC, or SRBC. The level of polyclonal antibody synthesis was correlated to the number of T. brucei injected and to the number of parasites in circulating blood. The observed B lymphocyte activation is not dependent upon the influence of T cells since infection of athymic nu/nu mice also led to polyclonal antibody synthesis. Stimulation of polyclonal antibody synthesis was also observed after T. brucei infection of C3H/HeJ mice, a strain of mice that is nonresponsive to bacterial lipopolysaccharides. Therefore, it is unlikely that the lipopolysaccharides component of endogenous Gram-negative bacteria play an important role in the observed proliferation and differentiation of B lymphocytes.
Autoimmune responses to DNA, red blood cells, and thymocyte antigens were observed in mice infected with T. brucei and the kinetics of their formation was parallel to the development of the polyclonal B cell activation.
Quantitative Measurement of C9 Sites and Their Association to the Ring-Like “Lesions” on Complement-Lysed Membranes: A Morphometric Immunoferritin Study
Authors: Rauterberg Ernst W. , Ungemach Bäurbel , Gebest Hans-Joachim 
Published: January 2023

Abstract
The appearance of ring-like “lesions” on negatively stained target membranes that had been subjected to complement (C) lysis was observed in the electron microscope more than a decade ago. However, it remained unclear whether the ring-like structures represent micelles or bubbles in the outer leaflet of the membrane or the lytic C5-9 complex itself. In the present work by immunoelectronmicroscopy and morphometric studies the ring-like structures were identified to contain C9, and thus seen to be identical to the proposed C5-9 complex.
EAC 1–9 membranes were incubated with rabbit anti-C9 antibodies followed by ferritin-labeled goat anti-rabbit IgG antibodies. More than 50% of the ring-like structures could be labeled by the staining system. The association of C9 to the C rings was statistically significant (p &lt; 0.001) as measured by two independent morphometric methods. About 50% of the C9-representing label could be observed with a greater distance than 300 Å apart from the C-induced ring-like structures. This finding may suggest that some of the ring-like structures are hidden on the membrane by their unfavorable position or that the ferritin label visualizes C9 not associated with ring-like structures. A possible diversity of the C5-9 complexes is discussed.
Physical Association of Histocompatibility Antigens and Tumor-Associated Antigens on the Surface of Murine Lymphoma Cells
Authors: Callahan Gerald N. , Allison James P. , Pellegrino Michele A. , Reisfeld Ralph A. 
Published: January 2023

Abstract
Serologic and immunochemical techniques were used to characterize plasma membrane antigens of the murine lymphoma 6C3HED. Syngeneic C3H/HeJ anti-6C3HED antisera were prepared and were shown by cytotoxicity, absorption, and immunoprecipitation tests to be specifically reactive with the lymphoma cells. Alloantisera to H-2.23 were found to be unreactive with intact lymphoma cells by cytotoxicity and absorption assays. However, H-2.23 antigens were detectable in tumor cell lysates by inhibition of cytotoxicity and immunoprecipitation. SDS-PAGE electropherograms of immunoprecipitates of radiolabeled tumor cell extracts obtained with anti-6C3HED and anti-H-2.23 antisera were essentially identical; proteins with Mr of approximately 70,000, 45,000, and 12,000 were apparent in both. An immunoadsorbent of insolubilized anti-6C3HED removed H-2.23 antigens detectable in lymphoma extracts, but had no effect on H-2.23 antigens in normal splenocyte extracts. These data indicate that H-2.23 and TAA are physically associated on 6C3HED cells.
Lymphocyte Stimulation with Fc Fragments
Authors: Berman Monique A. , Spiegelberg Hans L. , Weigle William O. 
Published: January 2023

Abstract
The effect of Fab and Fc fragments of immunoglobulins (Ig) of different species and different classes on DNA synthesis of mouse spleen cell cultures was analyzed by measuring 3H-thymidine incorporation. The data show that Fc fragments from mouse IgG induce strong stimulation of DNA synthesis in mouse spleen cells. In contrast, Fc fragments from turkey IgG are not stimulatory. The Fc fragments of all four human IgG subclasses, IgM, IgA1, and IgD, but not IgE, were stimulatory. In contrast, intact Ig and Fab fragments of the same classes had no effect.
Reduction and alkylation of the IgG Fc fragment did not diminish its activity. The pepsin fragment of IgG, pFc', which represents largely the Cγ3 domain, as well as a fragment obtained by trypsin cleavage of Fc also representing the Cγ3 domain, were both able to induce DNA synthesis. However, the activity of these subfragments was only between 10 and 25% of the activity of intact Fc, suggesting that sites in addition to the Cγ3 domain are required for optimal cell activation.
We postulate that enzymatic cleavage of Ig produces a mitogenically active Fc fragment with reactive sites similar to those of the Fc portion of Ig in antigen-antibody complexes or aggregated Ig. DNA synthesis induced by Fc fragments may represent a model of polyclonal lymphocyte activation through the Fc receptor.
Lactoperoxidase Catalyzed Radioiodination of Cell Surface Immunoglobulin: Incorporated Radioactivity May Not Reflect Relative Cell Surface Ig Density
Authors: Wilder Ronald L. , Chew Yuen Catherine , Mage Rose G. 
Published: January 2023

Abstract
Rabbit and mouse splenic lymphocytes were radioiodinated by the lactoperoxidase technique, extracted with non-ionic detergent, immunoprecipitated with high titered rabbit anti-kappa antisera, and compared by SDS-PAGE. Mouse sIg peaks were reproducibly larger in size than rabbit sIg peaks (often greater than 10 times). Neither differences in incorporation of label into the rabbit cell surface, nor differences in average sIg density explain this result. Total TCA-precipitable radioactivity was similar in each species. Estimation of the relative amounts of sIg in the mouse and rabbit showed similar average sIg densities. Differences in detergent solubility, proteolytic lability, or antisera used also do not adequately account for this difference. Thus, these data indicate that radioactivity incorporated after lactoperoxidase catalyzed cell surface radioiodination may not reflect cell surface Ig density. Conclusions about cell surface density based upon relative incorporation of radioactivity should be confirmed by other approaches.
Antigen-Specific Desensitization of Human Basophils
Authors: Sobotka Anne K. , Dembo Micah , Goldstein Byron , Lichtenstein Lawrence M. 
Published: January 2023

Abstract
Previous studies with isolated cell systems have shown desensitization (i.e., the induction of immunologic unresponsiveness after exposure to a stimulus under suboptimal conditions) to be antigenically nonspecific. Using pollen antigens and a bivalent penicillin antigen, [BPO]2, we found that, under conditions of passive sensitization, antigen-specific basophil desensitization occurred. Nonspecific desensitization always occurs with anti-IgE, and basophils of most atopic donors show nonspecific desensitization to antigens. Atopic donors were found, however, whose cells could be desensitized to one antigen while responding to noncross-reacting antigens and anti-IgE. Kinetic studies of desensitization revealed no differences between cells undergoing specific vs nonspecific desensitization. In the [BPO]2 system, removal of the antigen from the basophils by washing or by hapten ([BPO]1) competition did not reverse the specific desensitization to [BPO]2; passive replacement of specific IgE antibody did restore the response. Two types of desensitization, therefore, exist: 1) specific, which probably occurs due to the functional loss of some part of the IgE antibody-receptor complex and 2) nonspecific, involving the change noted above as well as an intracellular, biochemical alteration. Our data indicate that basophils with few IgE molecules undergo specific desensitization, whereas nonspecific desensitization occurs in basophils with many surface IgE molecules.
Binding of Antigen-Bearing Fluorescent Liposomes to the Murine Myeloma Tumor Mopc 315
Authors: Leserman Lee D. , Weinstein John N. , Blumenthal Robert , Sharrow Susan O. , Terry William D. 
Published: January 2023

Abstract
Small unilamellar lipid vesicles bearing the DNP-hapten on their surfaces and containing the water-soluble fluorescent dye carboxyfluorescein were formed by sonication. These vesicles were incubated with cells from the murine myeloma tumor MOPC 315, which secrete and also bear on the cell surface an immunoglobulin with affinity for the nitrophenyl hapten. At 0°C the cells bound an average of several thousand vesicles at saturation. This binding was specific for the nitrophenyl hapten on the vesicle since it was abolished by an excess of soluble nitrophenyl derivative, by omission of the hapten from the vesicle, or by substitution for MOPC 315 of a tumor lacking receptors for the nitrophenyl hapten. Specific binding of vesicles was greater when cells were incubated at 37°C.
The study suggests that ligand-bearing vesicles can be a useful marker for cell surface immunoglobulin. However, in spite of the ability to “target” vesicles to cell surface determinants, binding did not result in increased delivery of vesicle contents to the cytoplasm.
Reduced in Vitro Production of Anti-Tetanus Toxoid Antibody after Repeated in Vivo Immunization with Tetanus Toxoid
Authors: Stevens Ronald H. , Saxon Andrew 
Published: January 2023

Abstract
Lymphocytes from individuals booster-immunized with soluble tetanus toxoid synthesized anti-tetanus toxoid antibodies in vitro in the presence of pokeweed mitogen. The in vitro responsiveness initiated by day 14, peaked between days 20 and 40 and declined by days 60 to 80. Although the temporal kinetics of in vitro antibody production was similar in all individuals, the maximum levels of synthesis differed over an 8-fold range. The maximum quantity of anti-tetanus toxoid antibody synthesized in vitro after experimental immunization was correlated with the interval from prior booster immunization. Thus, cultures of B (0.4 × 106) and T (1.6 × 106) lymphocytes from individuals receiving the first immunization in ≥48 months synthesized up to 170 units of anti-tetanus toxoid antibody in vitro whereas individuals reboosted within 4 months of a prior immunization synthesized less than 40 units. This correlation was not observed with the in vitro synthesis of total IgG.
The in vitro anti-tetanus toxoid antibody response appeared to reflect in vivo production of antibody in that individuals receiving the first immunization in ≥48 months showed the greatest increase in serum antibody levels whereas a second booster immunization 4 months later caused only a slight increase in serum levels of anti-tetanus toxoid antibody. The decreased in vitro responsiveness after repeated immunization was not correlated with the suppressive activity of radiosensitive T lymphocytes but appeared to reflect decreased function of the non-T lymphocyte fraction. Removal of phagocytic cells did not increase in vitro anti-tetanus toxoid antibody production by lymphocytes from reboosted individuals.
Fc Receptors on Human T-Lymphocytes
Authors: Shaw Stephen , Pichler Werner J. , Nelson David L. 
Published: January 2023

Abstract
After in vitro allosensitization, human peripheral blood lymphocytes mediate specific allogeneic cell-mediated lysis (CML) and antibody-dependent cellular cytotoxicity (ADCC). To analyze the T lymphocyte subpopulations involved in CML and ADCC, lymphocytes were separated on the basis of their affinity for sheep erythrocytes (T cells), for Fc-IgM (TM cells), and Fc-IgG (TG cells) either before or after allosensitization. Subpopulations of T cells highly enriched for TM cells generated CML comparable to unseparated T cells, but subpopulations enriched for TG and effectively depleted of TM cells did not generate strong CML. Studies of CML generation by T cells exposed to immune complexes and by cocultured TM and TG cells failed to demonstrate any suppression by TG cells. Separation of subpopulations after allosensitization revealed that CML activity was mediated by T cells that lacked detectable Fc-IgG or Fc-IgM receptors. Parallel studies of ADCC revealed that the cytotoxic activity was depleted by removal of TG cells either before or after allosensitization. These studies demonstrate that a) TM cells contain precursors of CML effectors; b) TG cells are not required for the generation of CML; c) TG cells do not have marked suppressor activity in CML generation; d) TG cells contain ADCC effectors; and e) TM cells are not required for ADCC.
In Vitro Sensitization of Human Lymphocytes Against Histiocytic Lymphoma Cell Lines
Authors: Treves Abraham J. , Heidelberger Ellen , Kaplan Henry S. 
Published: January 2023

Abstract
Normal PBL were sensitized in vitro against an allogeneic diffuse histiocytic lymphoma cell line and their activity was measured by radiolabel release from target cells. We have reported earlier that a non-T cell population, found among the PBL, was responsible for inhibiting in vitro sensitization. In the present work we found that culturing PBL in vitro caused the induction of radioresistant suppressor cells which affected the sensitization phase of the in vitro response. The culture-induced suppressor cells had macrophage-like characteristics. The activity of the suppressor cells depended on an additional helper population that was adherent to nylon wool, but did not adhere to plastic and was nonphagocytic. The cooperation of these two different cell populations was required for the expression of suppressive activity.
The Late Phase Skin Reaction: Evidence for Activation of the Coagulation System in an IgE-Dependent Reaction in Man
Authors: deShazo Richard D. , Levinson Arnold I. , Dvorak Harold F. , Davis Robert W. 
Published: January 2023

Abstract
The late phase reaction (LPR), an IgE-dependent sequel to the wheal and flare response (WFR), was studied in ragweed (RW)-sensitive subjects 15 min and 6 to 8 hr after intradermal RW injection. The role of WFR in the genesis of LPR and LPR dependence on RW dose were determined by skin test titration to extinction of LPR. LPR size correlated with WFR size. LPR were noted with WFR as small as 9.5 ± 1.0 mm (S.E.M.) and RW doses as small as 0.01 protein nitrogen unit (PNU). In a group of WFR-positive but LPR-negative subjects, LPR were not induced despite increasing WFR to 18.2 ± 1.3 mm by simultaneous injection of RW + histamine (RW-H). Light microscopy of 1-µm biopsy sections of direct and Prausnitz-Kustner (P-K) LPR revealed a mixed cellular infiltrate qualitatively no different than that seen 6 hr after isolated WFR. Fibrin deposition in the absence of immunoglobulin or complement was seen by fluorescent microscopy in LPR but not in controls.
These data suggest that LPR may follow small RW doses. Furthermore, the failure of RW-H injection to induce LPR argues against a gatekeeper role for WFR in the genesis of LPR. The significance of the cellular infiltrate is not clear although fibrin deposition explains the clinical induration of LPR. This fibrin deposition is evidence for activation of the coagulation system in these IgE-dependent “delayed in time” reactions.
Studies of Congenitally Immunologic Mutant New Zealand Mice
Authors: Gershwin M. Eric , Castles James J. , Ikeda Richard M. , Erickson Kent , Montero John 
Published: January 2023

Abstract
Hereditarily asplenic (Dh/+) New Zealand Black (NZB) mice were produced by initial mating with B6CBA Dh/+ mice, followed by backcrossing, including H-2 typing and parental selection, with a colony of NZB mice. NZB Dh/+ mice, in their F6, F7, and F8 generation, were serially followed and compared to +/+ littermates. With age, NZB Dh/+ and +/+ mice develop a similar frequency of anti-erythrocyte and anti-nuclear, SS DNA, native DNA and poly I·poly C antibodies. Furthermore, renal histology is unchanged in NZB Dh/+ compared to +/+ mice. However, in striking contrast, NZB Dh/+ mice have a significantly reduced degree of hypergammaglobulinemia, a delayed onset and lower titer of naturally occurring thymocytotoxic antibody (NTA), and a reduction in both diffuse lymphocytic infiltrates and lymphoma. Moreover, although NZB Dh/+ mice lose a significant degree of T helper function with age, as manifest by reduced responsiveness to T cell mitogens, SRBC, and skin allografts, they appear to retain antigen nonspecific suppressor function. Thus, NZB Dh/+ mice develop autoimmune disease without influence by NTA and without premature loss of suppressor cell function. These results suggest that several of our present concepts regarding NTA, autoimmunity, and lymphoma in NZB mice need re-examination. Indeed, it appears that several features of NZB immunopathology, including development of NTA and lymphoma, are not directly related to the primary appearance of autoimmune disease.
Inhibition of Human Killer Cells by Autologous Lymphocytes
Authors: Pollack Sylvia B. , Emmons Sandra L. 
Published: January 2023

Abstract
Human antibody-dependent cellular cytotoxicity (ADCC) mediated by K cells is shown in this study to be inhibited by autologous lymphocytes. Inhibitor activity resides in a population of lymphocytes lacking Fc receptors, i.e., depletion of Fc receptor-bearing lymphocytes on immobolized enriches for inhibition. A T cell-enriched population does not inhibit. The effect is not steric inhibition since addition of large numbers of sheep or chicken erythrocytes does not decrease ADCC. Spontaneous cytotoxicity mediated by NK cells in the absence of added antibody is not inhibited by the FcR-depleted population, indicating that K and NK cells differ from each other in this respect.
Anti-tumor effects of allogeneic bone marrow transplantation in (NZB X NZW)F1 hybrids with spontaneous lymphosarcoma.
Authors: Moscovitch M , Slavin S 
Published: January 2023

Abstract
Untreated female (NZB X NZW)F1 hybrid mice (B/W F1) were found to develop lymphosarcoma spontaneously as they aged. Tumor incidence was evaluated in B/W F1 mice immunosuppressed with total lymphoid irradiation (TLI) and in TLI-conditioned B/W F1 mice reconstituted with 3 X 10(7) BALB/c bone marrow (BM) cells. BALB/C leads to B/W F1 chimerism (79 to 89% BALB/c-type cells) was confirmed by typing peripheral blood lymphocytes with specific alloantisera and complement by using a microcytotoxicity assay. Chimeras showed no clinical signs of graft-vs-host disease (GVHD). TLI-treated mice seemed to show a slightly accelerated onset of lymphosarcoma as compared with untreated controls, but the difference was not significant (p = 0.08). BALB/c leads to B/W F1 chimeras reconstituted at 1 to 3 mo of age (25 mice) developed no tumors for an observation period of 18 mo after transplantation. In contrast, tumors developed in 24/130 of age-matched controls, and in 13/57 of TLI-treated nonreconstituted age-matched B/W F1 mice. Tumor incidence in BALB/c leads to B/W F1 chimeras transplanted at an older age (9 to 11 mo) was similar to that observed in age-matched TLI-treated B/W F1 mice and age-matched untreated controls. The data suggests that the high naturally occurring incidence of lymphosarcoma could be reversed by reconstituting TLI-treated mice with BM cells (p = 0.027). Thus, allogeneic BM transplantation may exert potent graft-vs-tumor effects (GVT) when tumor susceptible hosts are reconstituted at an early age, whereas GVT is relatively ineffective at an advanced age, which probably correlates with an advanced stage of tumor development. Allogeneic BM transplantation should be additionally explored as a potential clinical tool for eradication of certain solid tumors in adjunct to high-dose radiochemotherapy, inasmuch as GVT seems to be independent of GVHD.
Thy-1 antigen expression by murine high-proliferative capacity hematopoietic progenitor cells. I. Relation between sensitivity to depletion by Thy-1 antibody and stem cell generation potential.
Authors: Boswell H S , Wade P M , Quesenberry P J 
Published: January 2023

Abstract
Hematopoietic stem cells of high proliferative potential such as the giant macrophage colony-forming cell HPP-CFC, were present in the marrow of mice treated with high dose 5-fluorouracil (5Fu) (150 mg/kg i.v.), whereas most committed granulocyte-macrophage progenitors, GM-CFU-C, were depleted. Enrichment of primitive stem cells in post 5-Fu bone marrow (5FuBM) was reflected in an enhanced capacity to proliferate in suspension cultures stimulated by the mixture of lymphokines present in Con A spleen-conditioned medium supernatant (Con A CM) when compared to normal bone marrow. The population of blast-like cells harvested at 5 days from suspension cultures of 5FuBM with Con A CM showed marked increases in stem cells GM-CFU-C and HPP-CFC. For this reason, 5FuBM was utilized to study the cell surface characteristics of putative pluripotential stem cells capable of giving rise to committed stem cells in suspension cultures. Treatment of 5FuBM (BDF1 mice) before suspension culture with a high concentration of either of two cytotoxic monoclonal antibodies directed against the Thy-1.2 surface antigen in the presence of rabbit complement reduced or abrogated the generation of stem cells HPP-CFC and GM-CFU-C in suspension cultures, even though the input content of HPP-CFC and GM-CFU-C in treated 5FuBM compared with control 5FuBM showed little reduction by the antibody plus complement treatment. The Thy-1+ cell required for generation of stem cells was not a T cell, because reconstitution of Thy-1.2-depleted 5FuBM with spleen nylon nonadherent (T) cells did not reconstitute the generation of stem cells, even though T cells did grow in the suspension cultures. In addition, depletion from 5FuBM of cells expressing Lyt-1 and Lyt-2 antigens, unambiguous markers of T cell-thymocyte differentiation, did not ablate the generation of HPP-CFC and GM-CFU-C. Rather, performance of Thy-1 cell depletion at lower efficiency, which still abrogated T cell function, ablated generation of HPP-CFC but did not affect the generation of GM-CFU-C. It was concluded that 5FuBM contains distinct Thy-1+ primitive stem cells expressing different amounts of Thy-1 antigen correlating with their respective generation potentials. Some of these Thy-1+ progenitor cells may be pluripotential.