bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro Tolerance Induction of Bone Marrow Cells: A Marker for B Cell Maturation
Authors: Metcalf Eleanor S. , Klinman Norman R. 
Published: December 2022

Abstract
B cell subpopulations have been defined by various morphologic criteria and differences in functional capacity. In a recent report from this laboratory, the in vitro splenic focus system was utilized to define a subpopulation of neonatal splenic B cells on the basis of their susceptibility to tolerance induction. Since this susceptibility to tolerance induction progressively decreases with age, tolerance susceptibility in this system has been attributed to the immaturity of the cells which constitute developing B cell clones. In the present study, the splenic focus technique was utilized to characterize the maturational state(s) of neonatal and adult bone marrow B cells as assessed by the susceptibility of these cells to tolerance induction, and to compare these responses to the responses of splenic B cells. The results demonstrate that the majority of neonatal bone marrow B cells reach maturity, by the criterion of tolerance susceptibility, later than splenic B cells. Furthermore, in contrast to the spleen, a portion (25%) of bone marrow B cells remain susceptible to tolerance induction even in the adult. Thus, the generative pool of B cells appears to shift from the spleen to the bone marrow after the first few days of neonatal life and resides primarily in the bone marrow thereafter. Finally, the susceptibility of B cells to tolerance induction may serve as a marker for the functional maturation of any given B cell population, and consequently may help to define distinct B cell subpopulations within the B cell pool.
Receptor-Binding Sites on C3 and C3b
Authors: Dierich Manfred P. , Bokisch Viktor A. 
Published: December 2022

Abstract
Human erythrocytes carry C3b receptors; Daudi lymphoid cells carry exclusively C3d receptors. With these two types of cells, it could be shown that isolated, uncleaved human C3 and soluble C3b possess two stable binding sites: SBS1-specific C3b receptors, and SBS2-specific for C3d receptors. Upon binding of freshly cleaved C3b (nascent C3b) via its labile binding site (generated on C3b through cleavage of C3) to the C3 acceptors on cell surfaces, the SBS2 becomes concealed. Kinetic experiments show that immediately after the action of fetal calf serum or partially purified C3b-inactivator on EAC1423b the SBS2 is accessible again. The reappearance of SBS2 does coincide with cleavage of surface-bound C3b into C3c and C3d but not with the release of C3c from the cell; C3c remains attached and is released only with delay. Concomitant with the cleavage event the number of SBS1 is reduced, stressing the importance of an unaltered steric configuration of the C3b structure for the expression of SBS1. An alternative explanation might be that the SBS1 is located at the site connecting C3c and C3d, so that it becomes altered upon dissection of the two fragments.
Complete Sharing of Light Chain Spectrotypes by Murine IgM and IgG Anti-Streptococcal Antibodies
Authors: Perlmutter Roger M. , Briles David E. , Davie Joseph M. 
Published: December 2022

Abstract
In order to examine the diversity of antibody light chains, we have developed an analytic isoelectric focusing procedure which permits the routine analysis of L chains from antibodies raised in individual mice. We have used this technique to demonstrate that the light chains of IgM and IgG anti-group A streptococcal antibodies raised in SWR mice are probably shared. Interestingly, numerous light chain spectrotypes are shared between individual mice whose 7S antibody focusing patterns differ.
The Mechanism of Activation of the First Component of Complement by a Univalent Hapten-IgG Antibody Complex
Authors: Goers John W. , Ziccardi Robert J. , Schumaker Verne N. , Glovsky M. Michael 
Published: December 2022

Abstract
We have previously shown that the univalent hapten, 2,4-dinitrophenyl (DNP)-polylysine when bound to anti-DNP-IgG antibody, yields a 7S complex which is a powerful activator of the classical pathway (Goers et al., 1975, J. Biol. Chem., 250:4918). In this paper we compare this univalent hapten-antibody complex with unassociated antibody, reduced and alkylated antibody, and IgG to which polylysine has been covalently attached. Of these, only the univalent hapten-antibody complex fixes complement. However, both antibody and reduced and alkylated antibody bind equally well to the C1q subunit of the first component, whereas only the univalent hapten-antibody complex shows enhanced binding to the intact first component, C1. Moreover, the antibody-hapten complex or hapten alone will bind to activate C1r,C1s to give C1̄r,C1̄s. The C1s, by itself, is not activated by hapten. Moreover, reassociated C1, composed of C1q,C1r,C1s, is activated by the hapten-antibody complex but not by hapten alone. These results allow us to postulate the existence of a polylysine-sensitive activation site on C1r,C1s which is concealed when C1r, C1s is associated with C1q. Furthermore, we suggest that the binding of hapten-antibody complex to C1 induces a conformational change which causes this site to become exposed. Finally, since all of the substances tested bind equally well to C1q, but only the hapten-antibody complex activates C1, we suggest that peripheral subunits on C1q serve only as anchors to bind C1 to antibody-coated cell surfaces or immune complexes and are not directly involved in the C1 activation process. Activation may occur, we speculate, when the antibody-hapten complex combines with the central stalk of C1q,C1r,C1s.
Molecular Control of B Cell Triggering by Antigen-Specific T Cell-Derived Helper Factor
Authors: Shiozawa C. , Singh B. , Rubinstein S. , Diener E. 
Published: December 2022

Abstract
Soluble, carrier-specific helper factor extracted from thymus-derived (T) cells primed to the carrier in vivo has been used to analyze the relationship between the degree of T cell help required to stimulate a primary antibody response in vitro and the molecular structure of the antigen. In order to define the conditions for optimal T cell help, we have constructed antigenic probes which consist of a number of serum proteins conjugated to a carbohydrate backbone. When these probes were trinitrophenylated for use as hapten-carrier conjugates to stimulate in vitro anti-TNP immune responses, we were able to define the conditions for optimal T cell help as one at which the carrier antigenic determinants are presented to the bone marrow-derived (B) cell in a closely spaced sequence. We suggest such a carrier focuses helper factor molecules by providing an array of determinants to which they can bind and then interact in a concentrated fashion with a small area of the B cell surface membrane.
When comparing the capacity of B cells to cooperate with helper factor from either syngeneic or allogeneic T cells, it was found that for a successful immune response to occur, both cooperating elements have to be of syngeneic origin. This extends the concept of allogeneic restriction between cooperating B and T cells to the level of interaction of soluble T cell-derived helper factor with B cells.
Myeloma-Specific Antibodies: Studies of Their Properties and Their Relationship to Tumor Immunity
Authors: Frikke Maureen J. , Bridges Sandra H. , Lynch Richard G. 
Published: December 2022

Abstract
The anti-idiotypic antibodies (a-Id315) induced in BALB/c mice by immunization with the dinitrophenyl (DNP)-binding, isologous myeloma protein produced by MOPC-315 were analyzed by double antibody radioimmunoassay to determine time of appearance, levels, heavy chain class, inhibitability with DNP-hapten, and relationship to MOPC-315 transplantation resistance. Following 200 µg of RA-315 per immunization, a-Id315 activity and MOPC-315 transplantation resistance were detected after the second of five weekly immunizations, and both increased after each subsequent immunization. After five weekly immunizations, individual sera from 180 mice were found to bind from 50 to 860 µg of 125I-RA-315 per ml. Approximately 95% of the a-Id315 detected after five weekly immunizations belonged to the IgG1 class, and the remaining 5% was IgG2a. Between 80 and 100% of the a-Id315 binding was inhibited by 3 × 10-3 M 2,4-DNP-L-lysine. Immunization schedules using increasing amounts of immunogen, from 5 to 200 µg, or increasing numbers of immunizations, from 1 to 4 showed that the induction thresholds for a-Id315 activity and the myeloma graft resistance were indistinguishable. When mice immunized with 200 µg of RA-315 weekly for 5 weeks were challenged with numbers of MOPC-315 cells sufficient to overcome transplantation resistance in 50 to 80% of the mice, none of the a-Id315 features analyzed differentiated resistant from nonresistant mice. Passive administration of a-Id315 serum did not influence the growth of MOPC-315 cells in normal syngeneic hosts. These observations suggest that the mechanism of idiotype-specific transplantation resistance observed in a-Id315-producing hosts probably involves more than the a-Id315 antibodies alone.
Antibody-Dependent, Eosinophil-Mediated Damage to 51Cr-Labeled Schistosomula of Schistosoma Mansoni: Effect of Metabolic Inhibitors and Other Agents Which Alter Cell Function
Authors: David John R. , Butterworth Anthony E. , Remold Heinz G. , David Peter H. , Houba Vaclav , Sturrock Robert F. 
Published: December 2022

Abstract
The effect of drugs known to inhibit different metabolic pathways or cell functions on antibody-dependent, eosinophil-mediated damage to schistosomula was determined. Eosinophil-mediated damage was completely inhibited by cytochalasin B, inhibitors of glycolysis, aminophylline, and treatment of cells with diazotized sulfanilic acid and tosyllysyl-chloromethyl ketone. The effects of cytochalasin and 2-deoxyglucose were reversible. On the other hand, eosinophil-mediated damage was unaffected by agents which inhibit DNA replication, protein synthesis, oxidative respiration, prostaglandin synthesis, and microtubule aggregation. The findings suggest that alteration of the cell surface membrane and microfilaments prevents damage by interfering with cell-target interactions, that energy derived from glycolysis is required for cytotoxicity, that cell-associated esterases are probably involved, and that cytotoxicity may be modulated by cyclic nucleotides. Some of the attributes of eosinophils that allow it and not other cells to mediate this reaction are discussed.
Negative Allogeneic Effects in Vitro
Authors: Swain Susan L. , Dutton Richard W. 
Published: December 2022

Abstract
Murine T cells can mediate a potent negative allogeneic effect on the capacity of primed cells to develop the secondary antibody-forming cell response to hapten carrier in vitro. This effect is detected when T cells confront responding cells differing at the major H-2 locus. The allosuppression is relatively sensitive to mitomycin treatment and to irradiation. The T cells responsible for the inhibition of antibody formation appear to express the Ly2 but not the Ly1 alloantigen. The secondary response of spleen cells in culture is quite insensitive to positive allogeneic effects. The usefulness of this model in elucidating the mechanism of allosuppression and the relevance of such effects to studies involving genetic restriction on cell interactions is discussed.
Temporal Regulation of the Immune Response to LDH-C4 by an X-Linked Gene in C3H/HeJ and SJL/J Mice
Authors: Marsh James A. , Wheat Thomas E. , Goldberg Erwin 
Published: December 2022

Abstract
Regulation of the immune response is a complex phenomenon under the control of many genes. This process may be analyzed by comparing the immunogenicity of structurally similar but distinct antigens. Both synthetic immunogens with limited numbers of determinants (1) as well as antigenically complex proteins (2, 3) have been used to study immunoregulatory mechanisms. The LDH iso zymes are particularly interesting because they display a high degree of structural similarity but can be distinguished immunologically.
Vertebrate LDH is a tetrameric enzyme. All tissues contain variable amounts of A (or M) and B (or H) subunits which randomly associate to produce five isozymes. The genetic control of the immune response to heterologous LDH-A and -B subunits has been studied in rabbits (4), rats (5), and inbred mice (6, 7). Antiserum to purified LDH-A4 or LDH-B4 reacts only with the isozymes containing the subunits used in immunization but not with the heterologous homotetramer (8, 9).
Letters to the Editor
Authors: Bigazzi Pierluigi E. 
Published: December 2022

Abstract
Dear Sir: We are flattered by the attention with which Dr. Junger has read not only our latest paper in the J.I., but also the other publications on BUF rat thyroiditis by our group. As you can imagine, we are very well aware of our previous reports on the incidence of thyroiditis in animals at 3 months of age or older. However, even in our recent review on spontaneous animal models of thyroiditis (1), we decided not to present a table such as the one Dr. Junger has compiled from our published data, because of the variability observed in several groups of animals. We have noticed thyroiditis at the age of 4 ± 1 months and this is the basis of our statement that the “disease appears first at the age of 4 months.”
With regard to the breakdown of disease by sex, we have indeed distinguished between sexes (see Table I), but because of the already too large number of tables we did not include these data in our J.I. paper.
Isolation of Receptor-Bearing Plasma Membrane Vesicles from Guinea Pig Macrophages
Authors: Scott Robert E. , Rosenthal Alan S. 
Published: December 2022

Abstract
The plasma membrane serves as an important site for the interaction of macrophages and lymphocytes in antigen recognition and of macrophages and foreign agents in inflammatory responses. Despite the critical role of the macrophage membrane in these reactions, studies on the biochemical and functional characteristics of macrophage membranes which need to be performed have been limited by the lack of suitable methods for the isolation of macrophage plasma membranes that maintain functional and antigenic membrane markers. Recently a new method for membrane isolation has been reported which is based on the observation that a variety of sulfhydryl blocking agents can induce the shedding of plasma membrane vesicles of monolayer cell lines. In this paper we demonstrate that guinea pig peritoneal exudate macrophages can also be induced to shed significant quantities of plasma membrane vesicles by such reagents, in particular with a low m.w. aldehyde, and that these vesicles can be isolated by centrifugation. Vesiculation in macrophages is potentiated by disulfide reducing agents, such as dithiothreitol, and by calcium ions. Maximum vesiculation is observed when well spread macrophage monolayers are incubated in a slightly hypertonic vesiculant at pH 7.0 for 2 hr at 37°C. Brief exposure of macrophages to a vesiculant for intervals as short as 30 min is also effective. Macrophage vesicles shed from the cell surface by this procedure have been found to contain receptors for concanavalin A, wheat germ agglutinin, phytohemagglutinin, and lentil lectin. Vesicles also contain Fc and complement (C3) receptors and form rosettes with thymic lymphocytes. It is suggested that macrophage plasma membrane vesicles isolated by this technique should serve as a valuable new system to study the biochemical characteristics of macrophage plasma membranes and their role in immunologic reactions.
Increased Binding and Killing of Neuraminidase-Galactose Oxidase-Treated Tumor Cells by Normal Macrophages
Authors: Piessens Willy F. 
Published: December 2022

Abstract
The binding of Line 10 hepatoma cells to normal syngeneic guinea pig macrophages is increased when the tumor cells are treated with neuraminidase and galactose oxidase (NAGO) before they are added to the macrophage monolayers. The effect is abolished by exposure of the NAGO-treated tumor cells to sodium borohydride.
Line 1 hepatoma cells treated with NAGO or with sodium periodate are killed to a greater extent than untreated tumor cells. This effect can also be reversed by sodium borohydride. Further, periodate-treated macrophages become cytotoxic for unmodified tumor cells.
These results demonstrate that increased tumor cell killing occurs when artificial contacts (presumably via Schiff bases) are established between normal macrophages and tumor cells. They are consistent with the hypothesis that close cell to cell contact is necessary for macrophage-mediated cytotoxicity.
Inhibition of Complement by Mouse Serum: Selective Inactivation of the Fourth Component of Human Complement
Authors: Mandle Robert J. , McConnell-Mapes Julia A. , Nilsson Ulf R. 
Published: December 2022

Abstract
Bound human C4b on EAC4 is rapidly inactivated in the presence of murine serum reagents. The functional characteristics of this inactivation suggest that it is probably caused by factor(s) homologous to human C3bI-C4bI: inactivation is temperature-dependent and occurs without concomitant consumption of the inactivator(s); loss of hemolytic function is associated with the cleavage of the bound C4b into C4c, which is released, and C4d, which is retained on the cell membrane. Murine serum reagents inhibit bound human C4b far more efficiently than C3b and may therefore be employed to selectively inhibit C4b.
Interactions of C-Reactive Protein with the First Component of Human Complement
Authors: Claus D. R. , Siegel J. , Petras K. , Osmand A. P. , Gewurz H. 
Published: December 2022

Abstract
C-reactive protein (CRP), a trace constituent of serum which generally increases dramatically in concentration during reactions of inflammation and tissue destruction, has recently been shown to inhibit multiple functions of both T cells and platelets. Certain interactions of CRP in the presence of human serum have been shown to result in the efficient depletion of C components C1-5, and in the initiation of C-dependent adherence, phagocytosis, and cytolysis. In the present experiments, CRP was compared with antibody for the ability to react with the first component of human complement. Like IgG, CRP was found to bind purified C1̄ and this binding was markedly enhanced upon chemical aggregation or interaction of CRP with one of its binding specificities, the C-polysaccharide (CPS) of the pneumococcus. Both hemolytically active and native CI bound to CPS-coated erythrocytes (ECPS) sensitized with CRP (ECPS-CRP), and in both instances C1̄ could be recovered by transfer to EAC4; approximately equivalent amounts by weight of CRP and rabbit anti-CPS were required for these effects. The interaction between CRP and C1̄ occurred at the level of C1q, as shown by inhibition of binding and transfer of C1̄ by purified C1q, agglutination of ECPS-CRP by C1q and binding of 125I-C1q to ECPS-CRP. Thus, these results provide further evidence for the similarity of CRP to antibody in the nature of its interaction with the first component of human complement at the level of C1q, and support the concept that CRP may have an important role in the initiation and modulation of reactions of inflammation and host defense.
The Role of Macrophages in the Generation of T Helper Cells
Authors: Erb Peter , Vogt Peter , Meier Barbara , Feldmann Marc 
Published: December 2022

Abstract
The generation of T helper cells in vitro requires macrophages or macrophage-derived factors such as genetically related macrophage factor (GRF) or nonspecific macrophage factor (NMF). However, there is a basic difference of T helper cell induction when using particulate antigens. The present study demonstrates that this difference is based on the activation of two different T cell subsets. GRF activates short-lived ‘T1’ cells which amplify the induction of T2 cells, which are the helper cell precursors. Thus, the genetic restriction of T helper cell induction seen with soluble antigen or GRF lies on the level of macrophage or GRF interaction with T1 cells. NMF (or macrophages) and particulate antigens directly activate the helper cell precursor (T2) indicating no requirement for T1-T2 cooperation. The direct activation of the helper cell precursor with particulate antigens does not require histocompatible macrophages or NMF from histocompatible macrophages.
The present results may explain some of the discrepancies reported in the literature concerning the genetic requirements and specificity of T cell activation.
Immune Suppression with Supraoptimal Doses of Antigen in Contact Sensitivity
Authors: Sy Man-Sun , Miller Stephen D. , Claman Henry N. 
Published: December 2022

Abstract
Immunologic suppression was induced in a mouse model of contact sensitization to DNFB by using supraoptimal doses of antigen. In these studies, in vivo measurement of ear swelling as an indication of immunologic responsiveness correlated well with measurement of in vitro antigen-induced cell proliferation.
This unresponsiveness was specific, since supraoptimal doses of DNFB did not interfere with the development of contact sensitivity to another contactant, oxazolone. The decrease in responsiveness is a form of active suppression, as lymphoid cells from supraoptimally sensitized donors transferred suppression to normal recipients. Furthermore, pretreatment with cyclophosphamide (Cy) reversed the suppression seen in supraoptimally sensitized animals but had no effect on the optimal sensitization regimen.
These results indicate that supraoptimal doses of contactants can activate suppressor cells and that precursors of these cells are sensitive to Cy. Such suppressors regenerate within 7 to 14 days after Cy treatment.
The ability of Cy pretreatment to affect supraoptimal sensitization without affecting optimal sensitization confirms other reports indicating that the observed results of Cy treatment depend critically upon the dose of antigen used.
Immunologic Aspects of Human Colostrum and Milk
Authors: Ogra S. S. , Weintraub D. , Ogra P. L. 
Published: December 2022

Abstract
A group of formula-fed infants were administered a single feed of poliovirus IgA antibody-rich human colostrum 18 to 72 hr after birth. Subsequently, the presence of IgG, IgA, and IgM immunoglobulin and poliovirus antibody activity was determined in serial serum and fecal samples of the neonates. Absorption of IgA immunoglobulin from the colostrum to the circulation was observed in three infants who were fed with colostrum between 18 and 24 hr after birth. Another group of infants of tuberculin-positive mothers who were being breast fed by their own mothers were followed for the development of in vitro correlates of cell-mediated immunity against tuberculin after prolonged breast feeding. Tuberculin-specific proliferative response was observed in the peripheral blood lymphocytes of two neonates after 5 weeks of breast feeding. The responses were undetectable after 12 weeks, although the infants continued to breast feed. No tuberculin reactivity was observed in the cord lymphocytes. These observations suggest uptake of IgA immunoglobulin and components of cellular immunity in the intestine during the immediate neonatal period.