bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular Cooperation and Stimulatory Factors in Antibody Responses: Limiting Dilution Analysis in Vitro
Authors: Vann Douglas C. , Dotson Carroll Ray 
Published: January 2023

Abstract
Limiting dilution analyses with the Poisson model were performed on normal mouse spleen cells alone or in the presence of added cells or soluble factors. When a constant number of T cells activated to sheep red blood cells were added to cultures of diluted spleen cells the mean frequency of response to sheep red blood cells was 5- to 30-fold greater than that of spleen cells diluted alone. Adding a constant number of B cells did not produce a significant change in the mean frequency of response of diluted spleen cells. Since a responding unit is thought to be composed of T cells and B cells, these results indicate that antigen-specific T cells normally limit the generation of responding units when normal spleen cells are subjected to limiting dilution analysis alone. Conversely, B cells appear to be in relative excess.
Culture medium supernatants from mixed cultures of T cells activated to histocompatibility antigens and target cells bearing the antigens to which the T cells have been activated enhance antibody responses in vitro. When spleen cells were diluted in the presence of added supernatants the mean frequency of response was increased relative to that of spleen cells alone. This is interpreted to mean that the supernatants contain a factor, or factors which replace the requirement for T cells and enhance in vitro antibody responses by enabling more B cells to participate in the response.
A Functional Abnormality of the Fifth Component of Complement (C5) from Human Serum of Individuals with a Familial Opsonic Defect
Authors: Nilsson Ulf R. , Miller Michael E. , Wyman Susanne 
Published: January 2023

Abstract
The nature of a familial opsonic defect of human serum was explored. Studies of the unseparated deficient serum indicated a functional abnormality of C5 despite the presence of C5 in normal amounts. Studies of the isolated C5 from opsonically deficient serum revealed a restricted, primary, functional defect analogous to the one suggested by the studies of unseparated C5 in the deficient serum: absent opsonic but normal hemolytic function. In addition a secondary, functional defect occurred in isolated deficient C5 upon prolonged handling at 4°C: hemolytic as well as -generated chemotactic activity was lost. There was no indication of an inhibitor or inactivator of C5, nor of an abnormality of C activation at levels other than that of C5 in deficient serum. These functional studies therefore verify our previous interpretation that the yeast opsonic defect reflects a functional defect or dysfunction of C5. No structural correlate for the functional abnormality of C5 has as yet been demonstrated in studies with the Ouchterlony technique, various modifications of the polyacrylamide gel electrophoretic procedure, as well as sucrose density ultracentrifugation.
Immune Responses in Vitro
Authors: Pierce Carl W. , Kapp Judith A. , Wood David D. , Benacerraf Baruj 
Published: January 2023

Abstract
The function of macrophages in the development of primary plaque-forming cell responses in cultures of mouse splenic lymphoid cells has been investigated. Splenic and peritoneal exudate macrophages are equally efficient in supporting development of responses by splenic lymphoid cells. The active cell in the peritoneal exudate population is a phagocytic macrophage. Macrophages have at least two distinct functions. One is to promote the viability or survival of splenic lymphoid cells in culture; this function can be duplicated by the reducing agent 2-mercaptoethanol. The second function is antigen presentation.
Rabbit Secretory IgA: Identification and Genetic Control of Two Allotypes of Secretory Component
Authors: Knight Katherine L. , Rosenzweig Miriam , Lichter Edward A. , Hanly W. Carey 
Published: January 2023

Abstract
Two allotypes of rabbit secretory IgA have been identified with antisera obtained by cross-immunization of rabbits with secretory IgA. The two antisera, anti-t61 and anti-t62, each reacted by double diffusion analysis with secretory IgA from some but not all rabbits. Both anti-t61 and anti-t62 reacted with purified free secretory component obtained from whey. Thus, anti-t61 and anti-t62 are identifying allotypic specificities on secretory component.
Genetic studies revealed that t61 and t62 are controlled by allelic genes at an autosomal locus. The t locus is not closely linked to the VHa, Cαf and Cαg (heavy chain) loci nor to the b (light chain) locus of immunoglobulins.
Release of Slow Reacting Substance of Anaphylaxis from Human Leukocytes
Authors: Grant J. Andrew , Lichtenstein Lawrence M. 
Published: January 2023

Abstract
Mediators of immediate hypersensitivity were released from human leukocytes by means of allergen challenge. Leukocytes from 12 consecutive donors were challenged with allergens to which these donors were clinically sensitive. In all, histamine and a second substance (SRS-Aleuk) which caused prolonged contraction of guinea pig ileum, were released. No SRS-Aleuk was obtained without allergen-challenge, and none was observed from non-atopic leukocytes challenged with the same allergens. The time of release after addition of allergens and the allergen dose-response curves for release of both histamine and SRS-Aleuk were quite similar. SRS-Aleuk was synthesized de novo after allergen-challenge since this factor was not demonstrated in disrupted cells. SRS-Aleuk was soluble in 80% ethanol and was not destroyed by base hydrolysis. The smooth muscle contracting activity of SRS-Aleuk resembled that of slow reacting substance of anaphylaxis (SRS-A) obtained from human lung and rat peritoneal cells, but was different from histamine, bradykinin, serotonin, and prostaglandin E1 and F2α. Preliminary studies suggest that both histamine and SRS-Aleuk are synthesized by human basophils.
We conclude that SRS-A is generated by human leukocytes as well as human lung and nasal polyps, and suggest that this mediator may play an important role in the pathogenesis of human immediate hypersensitivity reactions.
Preparation and Properties of Rabbit Anti-Mouse Plasmacyte Serum Purified by in Vivo Absorption: Further Evidence for a New Antigenic Determinant on Plasmacytes
Authors: Yutoku Masamichi , Grossberg Allan L. , Pressman David 
Published: January 2023

Abstract
A new surface antigenic determinant on both normal and malignant plasma cells of mice has been detected with rabbit antisera, obtained by immunization with mouse myeloma cells and purified by in vivo absorption. One IgG- and one IgA-producing myeloma was used. Although the determinant was detected on plasma cells and one lymphoma and not on other lymphoid cells, it was also found on cells of liver, kidney, and brain. Thus the antigen is not a plasmacyte-specific antigen. In spite of an apparent similarity between the tissue representation of the determinant and that of the PC.1 alloantigenic determinant, the present determinant is not identical with the PC.1 determinant, since it is found on the respective tissues of PC.1-negative strains of mice.
Acid Lability of Rhinoviruses: Loss of C and D Antigenicity after Treatment at pH 3.0
Authors: Hughes John H. , Chema Samson , Lin Nancy , Conant Robert M. , Hamparian Vincent V. 
Published: January 2023

Abstract
Serologic evidence is presented for the existence of rhinovirus antigens with C and D type reactivity, and for their loss after acid treatment. No neutralizing antibody could be detected in animal antisera prepared with pH 3.0-treated rhinovirus antigens. In contrast, antisera prepared with untreated (native) rhinovirus antigens, contained high levels of neutralizing antibody. In immunodiffusion tests, no precipitin lines were detectable when native antigens were diffused against antisera prepared with pH 3.0-treated antigens. Acid treated antigens also were non-reactive by immunodiffusion when reacted against antisera prepared with treated or untreated antigens. The diffusion of native antigens against hyperimmune animal sera prepared with untreated antigens gave one precipitin line. With normal human sera, two precipitin lines were observed with untreated antigens. Rhinoviruses and enteroviruses were found to share a common group reactive antigen.
Studies on the Structural and Conformational Basis for the Relative Resistance of Serum and Secretory Immunoglobulin a to Proteolysis
Authors: Underdown Brian J. , Dorrington Keith J. 
Published: January 2023

Abstract
The structural features which make secretory IgA relatively resistant to proteolysis, compared to the major serum immunoglobulin IgG, were investigated.
Secretory IgA, serum IgA, and IgG were incubated with pre-activated papain (4 hr) and Pronase (2 hr) at slightly alkaline pH in the absence of reducing agents. Digest mixtures were analyzed by Sephadex G-200 gel filtration and immunodiffusion. Under conditions which resulted in essentially quantitative cleavage of IgG1 myeloma proteins to Fab and Fc fragments, approximately 85% of secretory IgA, normal human serum IgA, and IgA myeloma proteins of both A1 and A2 subclasses remained undigested. Thus, both secretory IgA and serum IgA were relatively resistant to proteolysis compared to the major serum immunoglobulin, IgG1. Secretory IgA dimer was more resistant than IgA myeloma dimers since incubation with Pronase for 3 hr caused the depolymerization of the latter to a monomer-like fragment whereas secretory IgA dimer remained intact.
Reduction with 10 mM dithiothreitol (DTT) and alkylation of serum IgA caused this immunoglobulin to become susceptible to proteolysis. Secretory IgA required a greater concentration of reducing agent (35 mM DTT) for conversion to the digestible form than did IgA myeloma dimers. Circular dichroism was used to detect conformational changes in both serum and secretory IgA which occurred after mild reduction and alkylation. Part of the conformation change in IgA proteins after mild reduction and alkylation was localized to the Fc fragment.
It was concluded that secretory IgA was more resistant than the major serum immunoglobulin IgG1 and that this relative resistance was due in part to the greater resistance of immunoglobulin A per se, and in part due to additional stability of the secretory IgA form.
In Vivo Suppression by Cholera Toxin of Cell-Mediated and Foreign Body Inflammatory Responses
Authors: Warren Kenneth S. , Mahmoud Adel A. F. , Boros Dov L. , Rall Theodore W. , Mandel Mark A. , Carpenter Charles C. J. 
Published: January 2023

Abstract
Cholera toxin (CT) injected i.v. into mice resulted in a rise in cyclic AMP levels in splenic white cells. This was associated with and followed by a marked and relatively prolonged decrease in both the spleen cells and circulating lymphocytes. The effect of CT on a series of cell-mediated immunologic reactions related to the pathogenesis of schistosomiasis was then tested. CT profoundly suppressed dermal footpad swelling to soluble schistosome egg antigens, granuloma formation around schistosome eggs injected into the pulmonary microvasculature of unsensitized and sensitized mice, production of macrophage migration inhibition factor by intact granulomas (obtained from the livers of infected mice) maintained in vitro in tissue culture, and it ameliorated portal hypertension and esophageal varices in hepatosplenic schistosomiasis. In addition CT significantly prolonged allograft survival in mice even though it was first administered 6 days after grafting. Finally, CT completely eliminated foreign body granuloma formation around plastic beads (used as controls for the egg granulomas) which is a nonimmunologic reaction due to activation of chemical mediators of inflammation.
Conformational changes in C1q after binding to immune complexes: detection of neoantigens with monoclonal antibodies.
Authors: Golan M D , Burger R , Loos M 
Published: January 2023

Abstract
The formation of neoantigens within the C1q molecule after the binding of C1r and C1s to C1q and the binding of C1q to immune complexes is described. The neoantigens were detected by different monoclonal anti-C1q antibodies. This immunochemical study supports the hypothesis drawn from functional studies that the activation of the classical C pathway results from conformational changes within the C1q molecule leading to the activation of C1r and subsequently C1s.
Differential effect of activated T amplifier cells on B cells responding to thymus-independent type 1 and type 2 antigens.
Authors: Braley-Mullen H 
Published: January 2023

Abstract
Concanavalin A (Con A), antilymphocyte serum (ALS), and the allogeneic effect have all been shown to enhance antibody responses to thymus-independent (TI) antigens by a T cell-dependent mechanism. Enhancement presumably involves an effect on the responding B cells by amplifier T cells (TA) that are activated by the particular agent used, i.e., Con A, ALS, or allogeneic cells. In the present study the ability of these agents to augment antibody responses to TI-1 and TI-2 antigens was compared. It was found that antibody responses to TI-2 antigens were markedly enhanced by allogeneic cells or ALS given with antigen. Antibody responses to TI-1 antigens were in all cases unaffected. Because TI-1 and TI-2 antigens primarily stimulate separate subpopulations of B cells, these results suggest the B cell subset that responds to TI-1 antigens, i.e., Lyb-5-negative B cells, may not be responsive to signals from nonspecifically activated TA. This conclusion was further supported by experiments demonstrating that responses to TI-2 antigens could not be enhanced in mice that have only Lyb-5-negative B cells, i.e., CBA/N x BALB/c F1 males, and that responses to a T-dependent antigen (HRBC) could be augmented by the allogeneic effect in normal mice but not in mice lacking Lyb-5-positive B cells.
Expression of Lyt-1 by a subset of B lymphocytes.
Authors: Manohar V , Brown E , Leiserson W M , Chused T M 
Published: January 2023

Abstract
Using two-color flow cytometry and multiparameter data analysis, we have shown that the IgM bright, large subset of mouse splenic B lymphocytes express Lyt-1. This is not due to B cell uptake of immune complexes of Lyt-1 and antibody from T cells. The IgM bright cells of autoimmune NZB mice express more Lyt-1 than normal controls. This is because IgM containing plasmablasts, which are greatly increased in NZB spleens, are Lyt-1+. NZB spleen also contains more cells that are Lyt-1+ (but perhaps Lyt-1.2-), Thy-1.2 dull, and smaller in size than cells in normal mice. Thus, Lyt-1 is common to the T and B cell precursor or is induced independently during the ontogeny of T and at least one subset of B cells. We suggest that it be called Lyt-1.
A phorbol ester tumor promoter induces changes in the expression of immunoglobulins and DR antigens in human lymphoblastoid cells.
Authors: Roth P , Halper J P , Weinstein I B , Pernis B 
Published: January 2023

Abstract
The present study indicates that 12-O-tetradecanoyl phorbol 13-acetate (TPA) can induce either increases or decreases in the relative expression of membrane-associated IgM and IgD as well as the expression of other markers of lymphocyte differentiation on human B lymphoblasts, depending on the clone studied. The changes in membrane Ig expression are apparent within 24 hr and are maximal at about 48 hr after the addition of the compound. In clone BL, TPA decreases the membrane IgM/IgD ratio as determined by the percentage of cells bearing these isotypes and by their densities on single cells. In clone MW-E, TPA has the opposite effect. Although these changes are followed by an increase in Ig secretion by MW-E cells, measured by immunofluorescence and the protein A plaque assay, there is no induction of Ig secretion in BL cells. In addition, TPA increases the expression in BL of an additional B lymphocyte marker, the D region-related (DR) antigens, while having the opposite effect in MW-E. In two sublines of Daudi, a membrane IgM-positive, IgD-negative, nonsecreting cell line, TPA treatment resulted in the expression of membrane IgD without the induction of Ig secretion. Thus, the TPA-induced changes in the IgM/IgD ratio and DR antigen expression are inversely related and are not due to differential proliferation of subpopulations. Taken together, it appears that, depending on the particular clone of B lymphoblasts studied, TPA can induce or inhibit a coherent program of B lymphocyte maturation.
Production of macrophage-activating factor by T lymphocyte clones and correlation with other lymphokine activities.
Authors: Kelso A , Glasebrook A L , Kanagawa O , Brunner K T 
Published: January 2023

Abstract
The production of macrophage-activating factor (MAF) by antigen-stimulated murine T lymphocyte clones has been compared with their cytolytic function and release of other lymphokines. MAF activity was measured by the capacity of peptone-induced peritoneal exudate cells or bone marrow-derived macrophages to lyse 51Cr-labeled tumor cells after incubation with supernatant from the stimulated T cells and a nonactivating, amplifying dose of lipopolysaccharide. Of 72 clones generated against H-2, MIs, H-Y, or Moloney leukemia virus-associated antigens, 68 were found to produce detectable quantities of MAF. Release of MAF by clones 1) occurred within 1 to 12 hr of exposure to antigen, 2) required stimulation with cells of the relevant antigenic specificity, and 3) could also be induced by concanavalin A, indicating that the cloned cells were the source of the activity. The capacity of a clone to produce MAF was independent of its antigenic specificity, cytolytic activity, or ability to produce interleukin 2 or granulocyte-macrophage colony-stimulating activity. In contrast, production of interferon and MAF was not dissociated for any of the clones tested.
Estimate of the light chain repertoire size of fetal and adult BALB/cJ and CBA/J mice.
Authors: LeJeune J M , Briles D E , Lawton A R , Kearney J F 
Published: January 2023

Abstract
The potential light chain repertoires expressed by IgM antibodies of fetal liver and adult spleen cells were compared. B cells from these sources were stimulated by the polyclonal mitogen bacterial lipopolysaccharide and after 3 days were fused to construct hybridomas. The light chains synthesized by these hybridomas were isolated by electrophoresis and their heterogeneity was examined by isoelectric focusing. A total of 109 BALB/c and 77 CBA/J hybridoma-derived light chains obtained from fetal liver and adult spleen cells were analyzed in this way. Fifty-three and 45 unique light chains were obtained from BALB/c and C57BL/6 hybridomas, respectively. Some of these were repeated more frequently than others, but no significant differences were seen in the heterogeneity of the light chain spectrotypes of fetal and adult CBA/J and BALB/cJ mice. Furthermore, the kappa:lambda ratio of light chains were the same in fetal liver as adult-derived hybridomas. These results show that the heterogeneity of light chains as determined by IEF and the kappa:lambda ratio of IgM immunoglobulins is established very early in ontogeny.
Viral antigens act as helper determinants for antibody responses to cell surface antigens.
Authors: Bromberg J S , Lake P , Brunswick M 
Published: January 2023

Abstract
Thy-1 alloantigens on murine thymus cells are weak immunogens in vivo for PFC responses in the absence of other antigenic disparities between the donor and recipient. Our previous work showed that non-H-2 alloantigens acted as helper determinants to augment anti-Thy-1 PFC responses. In this report we demonstrate that strong helper antigens are also produced by infection of donor thymus cells with viruses such as HSV-1, NDV, or vaccinia. This helper effect (as much as 30-fold) for a cellular antigen, requires linked recognition (expression of Thy-1 and virus in the same cell membrane), is T-dependent, antigen- (virus) specific, and is Thy-1-specific. The recognition of the viral helper sites is not restricted by the MHC genotype of the thymus cell donor, indicating that host reprocessing of antigen occurs. These are the first results that show that adventitious antigens may function as helper determinants for antibody responses to native membrane antigens and may be the mechanism that initiates several forms of acute post-viral autoimmune disease.
Induction of transplantation tolerance in guinea pigs by spleen allografts. II. Responses in the mixed leukocyte reaction correlate with the tolerant state.
Authors: Shevach E M , Chan C , Bitter-Suermann H 
Published: January 2023

Abstract
We have developed a model for the induction of transplantation tolerance in the guinea pig by vascularized spleen allografts. Spleen allografts from strain 13 to strain 2 hosts frequently survived in healthy recipients without clinical GVHD or induced clinical GVHD. (2 x 13)F1 to strain 2 spleen allografts survived indefinitely without inducing GVHD. In contrast, strain 2 spleen allografts were rejected by strain 13 hosts. An excellent correlation was observed between the clinical course and the degree of reactivity to donor strain stimulator cells in the MLR. Animals that had rejected their grafts had normal or enhanced proliferative responses in the MLR. Strain 2 hosts with long-term surviving strain 13 or (2 x 13)F1 grafts had markedly suppressed anti-13 responses. Animals with GVHD had a suppressed MLR toward donor strain stimulator cells with simultaneous reactivity to host strain stimulator cells. Cells capable of suppressing the response of normal host strain cells to donor strain stimulators were present in some long-term surviving animals and may be responsible in part for the maintenance of the tolerant state.
Autoimmune effector cells. III. Role of adjuvant and accessory cells in the in vitro induction of autoimmune encephalomyelitis.
Authors: Killen J A , Swanborg R H 
Published: January 2023

Abstract
The present investigation shows that autoreactive effector cells that transfer experimental allergic encephalomyelitis (EAE) can be activated from spleens and lymph nodes of Lewis rats given a single injection of 25 micrograms myelin basic protein (BP) in incomplete Freund's adjuvant (IFA), despite the fact that the cell donors do not develop EAE. Rather, these donor rats are unresponsive to EAE when given an encephalitogenic emulsion of BP in complete Freund's adjuvant (CFA). Lymphoid cells from rats given a single injection of BP-IFA were almost as effective as cells from BP-CFA-treated rats with respect to transferring EAE after in vitro activation with BP or concanavalin A (Con A). Irrespective of whether donors received BP in IFA or CFA, BP-cultured spleen and lymph node cells (SpC and LNC, respectively) transferred EAE, whereas Con A-cultured SpC but not LNC exhibited effector cell activity. Con A-cultured LNC were able to transfer EAE if the cultures were reconstituted with irradiated adherent phagocytic cells (which could be obtained from normal Lewis rat spleens) or with conditioned medium from these adherent SpC. These findings indicate that accessory cells are required for in vitro induction of this T cell-mediated autoimmune response.
Rabbit anti-human CSF IgG. I. Characterization of anti-idiotype antibodies produced against MS CSF and detection of cross-reactive idiotypes in several MS CSF.
Authors: Tachovsky T G , Sandberg-Wollheim M , Baird L G 
Published: January 2023

Abstract
Serum from rabbits injected with IgG prepared from the CSF of patients with multiple sclerosis were rendered anti-idiotypic by adsorption on sequential columns of pooled human gamma-globulin, free light chains and free heavy chains. Adsorbed antisera precipitated between 15% and 45% of the autologous ligand and were inhibited by autologous CSF and serum and F(ab')2 fragments prepared from serum IgG. Idiotypic cross-reactivities were detected among the CSF IgG of several MS patients using three of these antisera. Two antisera demonstrated low levels of cross-reactivity with CSF IgG obtained from two of six heterologous MS patients. The third antiserum detected highly cross-reactive idiotypic determinants in the CSF IgG of two family members both having MS.