bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo maturation of pre-B cells derived from long-term cultured bone marrow.
Authors: Nagasawa R , Kanagawa O , Tittle T V , Chiller J M 
Published: December 2022

Abstract
Long-term culture of a nonadherent pre-B cell line was established from BALB/c bone marrow by the method of Whitlock and Witte. Adherent filler cells, also derived from bone marrow, were required for the growth of such pre-B cells. The surface phenotypes of the nonadherent cells determined by FACS analysis were negative for mu-chain, kappa-chain, and Ia, but 50% of nonadherent cells expressed a marker recognized by the monoclonal 14.8. Analysis of cytoplasmic immunofluorescent staining revealed the presence of cytoplasmic mu-chain but absence of kappa-chain. These pre-B cells did not respond in vitro to such mitogens as LPS or DxSO4 and were not stimulated by allospecific helper T cells. However, when such BALB/c derived pre-B cells were transferred to irradiated BDF1 mice, recovered spleen cells expressed mu-chain as well as the marker recognized by 14.8. Such in vivo passaged pre-B cells were able to respond to LPS in vitro. Moreover, the response observed was diminished markedly by anti-H-2d antiserum and complement (C) but not anti-H-2b and C, indicating that the responder cells were of donor rather than host origin. Because the reconstitution of irradiated mice was limited to cells of the B lymphocyte lineage, it would appear that cells recovered from in vivo passage are the progeny of in vitro cultured pre-B cells and not that of in vitro contaminating stem cells.
The B cell surface molecule B1 is functionally linked with B cell activation and differentiation.
Authors: Tedder T F , Boyd A W , Freedman A S , Nadler L M , Schlossman S F 
Published: December 2022

Abstract
The B1 molecule is a 32,000 m.w. phosphorylated cell surface protein expressed exclusively by B cells from the mid pre-B until the plasma cell stage of differentiation. Two monoclonal antibodies (gamma 2a and mu) reactive with this molecule were used to assess the role of B1 in B cell activation, proliferation, and differentiation. The anti-B1 antibodies at concentrations ranging from 0.1 to 100 micrograms/ml significantly inhibited B cell proliferation induced by anti-mu antibodies, Staphylococcus aureus Cowan strain 1, activated T cells, and Epstein Barr virus. Although capable of inhibiting proliferation, anti-B1 antibody in soluble form or coupled to beads did not activate B cells or induce proliferation. Antibodies of comparable isotypes or against other B cell-restricted antigens, including B2, B4, B5, and HB-5, did not inhibit activation. Pretreatment of B cells with anti-B1 antibody did not inhibit activation, indicating that B cells had to be cultured with anti-B1 antibody for anti-B1-mediated inhibition to occur. Maximum inhibition was obtained when anti-B1 antibody was added at the initiation of culture. In agreement with this, growth factor-dependent proliferation of preactivated B cells was not inhibited by anti-B1 antibodies. Comparable inhibition of B cell activation was noted with antibodies reactive with class II antigens of the major histocompatibility complex with the exception that anti-B1 antibody inhibited immunoglobulin secretion in pokeweed mitogen assays, whereas anti-DR antibody did not. These results suggest that the B1 molecule may serve a central role in the regulation of B cell activation and differentiation.
Different antigen-presenting cells differ in their capacity to induce lymphokine production and proliferation of an apo-cytochrome c-specific T cell clone.
Authors: Baumhüter S , Bron C , Corradin G 
Published: December 2022

Abstract
The activation of an apo-cytochrome c-specific T cell clone was found to differ, depending on the antigen-presenting cell population. Whereas total syngeneic spleen cells and bone marrow macrophages could be shown to trigger proliferation, IL 2, and MAF production by the T cell clone, a B cell lymphoma only induced MAF secretion. Further studies demonstrated that this effect was not due to a different antigen processing by the B lymphoma or to limiting amounts of Ia and antigen molecules on the B lymphoma cell surface. The dissociation of induction of MAF production from IL-2 production/proliferation found with the different antigen-presenting cells indicates strongly that molecules other than Ia and antigen may be required for the complete functional activation of antigen-specific T cell clones.
TNP-specific Lyt-2+ cytolytic T cell clones preferentially respond to TNP-conjugated epidermal cells.
Authors: Shimada S , Katz S I 
Published: December 2022

Abstract
A most effective method for the induction of hapten-specific allergic contact sensitivity (CS) is via epicutaneous application of the hapten. Another effective method is by the administration of haptenated epidermal cells (EC) subcutaneously. The latter method induces more intense and longer lasting CS than does the subcutaneous administration of haptenated spleen cells (SC). Thus, there may be something unique about EC which, when haptenated, allows them to generate effector cells more effectively than do SC. We therefore attempted to generate T cell clones that were both hapten- and epidermal-specific. Four days after painting mice with 7% trinitrochlorobenzene, draining lymph node cells were obtained and T cells were purified. These cells were co-cultured with trinitrophenylated (TNP) Langerhans cell-enriched EC. After 4 days, cells were harvested and rested on non-TNP-conjugated EC. The cells were restimulated and rested three times, and were then cloned by limiting dilution with added interleukin 2, which was then continually added. Proliferation of T cells was assessed by [3H]-thymidine incorporation. Cytotoxicity assays utilized TNP-conjugated concanavalin A SC blasts or EC as targets. Clones A-2 and E-4 are Thy-1+, Lyt-2+, and L3T4-, and TNP-specific. In contrast to noncloned TNP-specific T cells, the clones proliferate preferentially in response to TNP-EC rather than TNP-SC. Also in contrast to noncloned T cells, the clones were preferentially cytotoxic for TNP-EC; compared to TNP-SC, there was an eight- to 32-fold increase in killing when TNP-EC were used as targets. Clones A-2 and E-4 therefore exhibit hapten and epidermal specificity. The epidermal-specific epitope that is recognized is unknown, but genetic restriction and antibody inhibition studies indicate that it is co-recognized with H-2K.
T cell regulation of light chain expression: preferential enhancement of Ig kappa production by T cells in the response to DNP.
Authors: Burkly L C , Wortis H H 
Published: December 2022

Abstract
We have reported that the relative amounts of Ig kappa and Ig lambda anti-DNP antibodies produced depend on the molecular form in which the hapten was presented. Here we confirm this finding by demonstrating that 1) the effects of adjuvant are not sufficient to result in differential light chain production and 2) the presence of some DNP-containing epitopes unique to DNP-KLH are not sufficient to give rise to enhancement of Ig kappa production. We further demonstrate that preferential augmentation of Ig kappa in the response to DNP is a T cell-mediated effect. Although we cannot rule out the possibility that some Ig kappa antibodies specific for protein-conjugated DNP require T cells for their expression, one of several other possible mechanisms whereby T cells influence light chain production is considered likely.
Genetic and biological characterization of a T suppressor cell induced by anti-idiotypic antibody.
Authors: Monroe J G , Gurish M , Dambrauskas J , Slaoui M , Lowy A , Greene M I 
Published: December 2022

Abstract
The cellular and molecular characteristics of anti-idiotype-induced suppression have been investigated. We have shown that i.v. immunization of A/J or C.AL-20 mice with rabbit antibodies against the major cross-reactive idiotype on A/J anti-ABA antibodies induces splenic suppressor T cells (Ts) able to suppress T cell-mediated cytolytic and delayed-type hypersensitivity responses to ABA. In these studies, we compare the T suppressor activity manifested by anti-Id-induced suppressor cells with that described previously after conventional antigen priming. Results indicate that i.v. injection of anti-idiotypic antibodies primes for efferent level Ts; in contrast, i.v. administration of ABA-coupled cells induces afferent level suppressor cells. Soluble cell lysates, containing suppressor factor(s) derived from these anti-idiotype-induced Ts, can also mediate suppression of T cell immune responses in an efferent manner. Factor-mediated suppression is MHC-unrestricted and is also observed in mice pretreated with cyclophosphamide, suggesting that this activity is analogous to third-order suppression. Furthermore, this factor suppresses the T cell-mediated DTH and CTL responses in an antigen-nonspecific but Igh-restricted manner. These latter results suggest that the cellular elements conferring antigen specificity and Igh restriction are separate. The implications of these findings to the relationship between idiotypic elements, antigen-binding structures, and Igh restriction elements on immunoregulatory T cells are discussed.
Analysis of a TH1----TH2 helper cell circuit.
Authors: McNamara M , Kang C Y , Kohler H 
Published: December 2022

Abstract
In the present study, the T15 idiotype-recognizing T helper cell circuit was dissected with respect to its homeostasis, interactive specificity, stability over time, and effects on B cell expression. Analysis of the TH1 cells by adoptive transfer experiments indicates their short-lived state of activity, during which TH2 cells are stimulated. TH1 cell activity was also directly monitored by the use of TNP-anti-T15 hybridoma antigens. It was found that TH1 cells are detected 1 wk after priming with PC-Hy, whereas TH2 cells become activated after 4 wk of priming. Comparative analysis of TH1 cells by using two different TNP-anti-T15 hybridoma antigens indicates a TH1 specificity for a shared idiotope. The stability over time of the TH1----TH2 circuit was demonstrated by comparing TH2 frequencies in young and old mice. Finally, we addressed the question of the function of the idiotype-recognizing T helper cells and showed that stimulation of T15-idiotype-specific TH2 cells can be correlated with a significant increase in the percentage of T15 idiotype in an anti-PC response. Collectively, these data describe an idiotype-specific T helper circuit as part of the network homeostasis of the immune system.
Specificity, phenotype, and precursor frequency of primary cytolytic T lymphocytes specific for class II major histocompatibility antigens.
Authors: Golding H , Singer A 
Published: December 2022

Abstract
Most cytolytic T lymphocytes (CTL) recognize class I rather than class II MHC determinants, and relatively little is known about those CTL that do recognize class II MHC determinants. The present study was undertaken to document the specificity, phenotype, and precursor frequency of primary class II allospecific CTL. It was found that class II-allospecific CTL could be consistently generated in vitro from unprimed spleen or thymus populations in the presence of exogenously added helper factors. The class II MHC specificity of both the precursor and CTL effectors activated in primary cultures by Ia-disparate stimulator cells was documented both by blocking experiments with anti-Ia mAb and by the use of L cell transfectants. The mechanism by which primary allospecific CTL effectors lysed their targets appeared to involve direct cell-cell contact, because they failed to lyse bystander target cells. The frequency in unprimed spleen populations of precursor CTL specific for class II alloantigens was examined by limiting dilution analysis and was found to be as high as 1/15,000 splenocytes and approximately 10% of the frequency reported for primary class I allospecific CTL. Finally, the Lyt phenotype of primary class II allospecific CTL precursors and effectors was determined. It was found that anti-class II CTL derive from at least two distinct precursor subpopulations that are either L3T4+Lyt-2- or L3T4-Lyt-2+, and that the Lyt phenotype expressed by the CTL effectors are concordant with that of their precursors. No correlation was found between the I subregion gene products recognized by CTL effectors and the Lyt phenotype they expressed in that both I-A- and I-E-specific CTL were both L3T4+Lyt-2- and L3T4-Lyt-2+.
The distribution of the Qa-2 alloantigen on functional T lymphocytes.
Authors: Hogarth P M , Basten A , Prichard-Briscoe H , Henning M H , Sutton V R , McKenzie I F 
Published: December 2022

Abstract
The expression of Qa-2 on functional lymphocytes was investigated in vitro and in vivo by using a monoclonal anti-Qa-2 antibody. In vitro treatment of T cells with antibody and complement demonstrated that T cells mediating help or delayed-type hypersensitivity for anti-SRBC responses were Qa-2+. In addition, cytotoxic T cells and either their precursors or cells involved in their generation were Qa-2+, as were anti-HGG suppressor T cells. Panning techniques were also used to show that secondary suppressor T cells were Qa-2+ and that there may be heterogeneity in suppressor T cells defined by Qa-2 expression. In vivo treatment of mice with anti-Qa-2 resulted in decrease in immune responsiveness seen by i) prolongation of skin grafts with either H-2D or I-A differences, ii) suppression of delayed-type hypersensitivity, and iii) inhibition of T cell-mediated suppression. Finally, IgG, but not IgM, anti-body-forming cells were Qa-2+.
Failure of PFC inhibition assays to distinguish idiotypically between clonotypes that are readily distinguishable by RIA analysis.
Authors: Schepart B S , Mayers G L , Bankert R B 
Published: December 2022

Abstract
Two different hemolytic plaque assay protocols that are commonly used to quantitate idiotype-positive antibody-secreting cells have been compared to a standard radioimmunoassay (RIA) to test for their ability to discriminate between related, but idiotypically distinct, clonotypes. The idiotype proband used in this analysis is the individual specific idiotype associated with the dextran-binding myeloma protein M104E (M104E IdI). Antibodies specific for this private idiotype (anti-M104E IdI) were purified by a combination of adsorption and affinity chromatography of the immunoglobulin fraction isolated from the sera of rabbits repeatedly immunized with M104E. The same affinity-purified anti-M104E IdI antibodies were used in the hemolytic plaque assays and in the RIA. In one of the plaque assays, the putative idiotype-positive antibody-forming cells were scored by lysis of target erythrocytes to which the anti-idiotype had been covalently coupled. In the other plaque assay, the idiotype-positive cells were determined indirectly by anti-idiotype inhibition of PFC produced on dextran-coupled target erythrocytes. The fidelity of these two assays to quantitate the M104E private idiotype expression in individual BALB/c mice after a single immunization with dextran B-1355S was determined by comparing the plaque assay data to the data generated by a double-antibody, post-precipitation RIA of either the antibodies in the serum or of monoclonal antibodies produced by hybridomas. Our data indicate that both plaque assay protocols reflect an overestimate of the actual expression of M104E private idiotype. By using a library of dextran-specific hybridomas (that have been characterized in an RIA with respect to their M104E IdI cross-reactivity), we have shown that the PFC overestimate of the M104E expression observed in dextran-immune mice is due to the inability of both plaque assay protocols to distinguish between dextran-specific clonotypes that express idiotypes cross-reactive with, but not identical to, the 104E IdI. We conclude that the plaque assay should be used only in conjunction with an RIA to estimate the idiotype expression. This is especially true in situations where closely related cross-reactive idiotype families exist.
Antibody response of BALB/c mice to dextran B1355S: alterations in the expression of an idiotype associated with the depletion of idiotype-binding cells.
Authors: Schepart B S , Abu-Hadid M , Mayers G L , Bankert R B 
Published: December 2022

Abstract
In this study, we established that BALB/c mice recognize and respond to the idiotype (M104E IdI) of a major dextran-specific clonotype within the BALB/c mouse repertoire. This idiotype recognition is established by demonstrating the presence of idiotype-binding cells and by the production of antibodies specific for the private M104E idiotype. To determine whether or not the idiotype-recognizing cells play a regulatory role during an immune response to dextran, the idiotype-binding cells were selectively removed either by panning or by radiation-induced killing. Two significant effects are observed when the depleted spleen cells are immunized with dextran. First, there is a substantial increase in the proportion of anti-dextran antibodies that are M104E IdI+. The second effect of the idiotype-specific cell depletion is the production of significant amounts of M104E IdI+ immunoglobulin molecules which do not bind dextran. The depletion experiments produced no alteration in the concentration of anti-dextran antibodies found in the serum or in the number of dextran-specific PFC in the spleen. The data indicate that idiotype-reactive cells can play a role in regulating the level of individual clonotype expression (i.e., the M104E clonotype), but that an alternative mechanism must exist for regulating the absolute amount of anti-dextran antibody produced after immunization.
Lymphokine-activated killer cells are generated before classical cytotoxic T lymphocytes after bone marrow transplantation in mice.
Authors: Merluzzi V J , Savage D M , Smith M D , Last-Barney K , Mertelsmann R , Moore M A , Welte K 
Published: December 2022

Abstract
Lymphokine-activated killer (LAK) cells are demonstrable within 2 wk after syngeneic or allogeneic (H-2-compatible) bone marrow transplantation in mice. Classical cytotoxic T lymphocytes (CTL) are not active until at least 4 wk after transplant. Both LAK cells and CTL bear the Thy-1 marker and do not possess the murine natural killer cell marker asialo GM.
Reactivity of anti-mitochondrial autoantibodies in primary biliary cirrhosis: definition of two novel mitochondrial polypeptide autoantigens.
Authors: Frazer I H , Mackay I R , Jordan T W , Whittingham S , Marzuki S 
Published: December 2022

Abstract
Sera that contained autoantibodies to mitochondria (AMA) by immunofluorescence were examined by immunoblotting for reactivity with mitochondrial polypeptides from various mammalian species, yeast, and E. coli. Mitochondrial polypeptides were separated by polyacrylamide gel electrophoresis, were immobilized on nitrocellulose, and were exposed to sera. The sera tested included 18 AMA-positive sera from patients with primary biliary cirrhosis (PBC), two AMA-positive sera from patients without PBC, and 53 AMA-negative sera. All AMA-positive sera reacted with either one or the other, or usually both of two human mitochondrial polypeptides of 70 kilodalton (kD) and 45 kD. The 53 AMA-negative sera were not reactive with the 70 kD polypeptide, but six reacted with the 45 kD polypeptide. The reactivity of the 70 kD and the 45 kD polypeptide was destroyed by brief exposure to trypsin. The counterpart of the 70 kD reactive polypeptide in human mitochondria was a 65 to 70 kD polypeptide in rat and mouse mitochondria, and a 55 kD polypeptide in yeast and in E. coli. The apparent 45 kD polypeptide was similar in all mitochondrial preparations tested, but no counterpart could be identified in E. coli. Beef heart mitochondria were used to show that the reactive polypeptides were present in a semipurified preparation of the F1 portion of mitochondrial H+ ATPase; however, sera did not react with the beta subunit of ATPase, proposed as a candidate mitochondrial autoantigen. The present molecular characterization of two particular antigens should lead to the more precise identification of these antigens, and also to a clearer insight into the pathogenesis of PBC.
Mechanisms of human T cell response to mitogens: IL 2 induces IL 2 receptor expression and proliferation but not IL 2 synthesis in PHA-stimulated T cells.
Authors: Katzen D , Chu E , Terhost C , Leung D Y , Gesner M , Miller R A , Geha R S 
Published: December 2022

Abstract
Human peripheral blood T cells were purified by a four-step procedure which included depletion of plastic-adherent cells, rosetting with sheep red blood cells, nylon wool passage, and treatment with mouse monoclonal antibodies to human Ia antigens plus complement. The purified T cells completely failed to proliferate to phytohemagglutinin (PHA). Bacterially derived recombinant human interleukin 2 (IL 2) reconstituted the proliferative response of resting T cells to PHA. The optimal concentration of IL 2 required was 100 to 200 U/ml. IL 2 alone caused no T cell proliferation. Both PHA and IL 2 needed to be present together for the proliferation of T cells to occur. Incubation of T cells with either PHA or IL 2 alone for up to 18 hr, followed by washing, then by the addition of the reciprocal reagent, resulted in no T cell proliferation. Expression of IL 2 receptors and of Ia antigens, as assessed by indirect immunofluorescent staining, revealed that both PHA and IL 2 needed to be present for Tac and Ia antigen expression by T cells. T cells incubated with PHA and IL 2 for 18 to 42 hr acquired responsiveness to IL 2. These T cells remained absolutely dependent on IL 2 for proliferation to occur. In contrast to T cells stimulated with PHA in the presence of monocytes, T cells stimulated with PHA and IL 2 released no detectable IL 2. The failure of IL 2 secretion was not caused by down-regulation of IL 2 production by IL 2 itself, because the addition of IL 2 to cultures of T cells stimulated with PHA in the presence of monocytes did not interfere with IL 2 production. These results indicate that IL 2 is a sufficient signal to induce the expression of its receptor in PHA-stimulated T cells and subsequent proliferation but is not sufficient to cause endogenous IL 2 release.
Regulation of IFN-gamma induction in human peripheral blood cells by exogenous and endogenously produced interleukin 2.
Authors: Vilcek J , Henriksen-Destefano D , Siegel D , Klion A , Robb R J , Le J 
Published: December 2022

Abstract
Interferon (IFN)-gamma production, stimulated by the addition of exogenous interleukin (IL) 2, T cell mitogens, or tuberculin purified protein derivative (PPD) was studied in cultures of separated human mononuclear cells or unseparated peripheral blood leukocytes (PBL). IFN-gamma was induced by the addition of IL 2 to cultures of otherwise unstimulated cells. The minimal concentration of exogenous IL 2 required to cause a reproducible stimulation of IFN-gamma was about 10 U/ml, i.e., approximately 50 times the minimal concentration required to stimulate proliferation in an IL 2-dependent murine cytotoxic T cell line. Approximately 500 to 1000 IL 2 U/ml were required to produce maximal stimulation of IFN-gamma production in otherwise unstimulated cultures. Monoclonal antibody anti-Tac, specific for an epitope associated with the IL 2 receptor (IL 2 R), inhibited IFN-gamma induction by exogenous IL 2 less strongly than induction by phytohemagglutinin (PHA) or concanavalin A (Con A). The highest degree of inhibition was exerted by anti-Tac on IFN-gamma production stimulated with PPD. Stimulation of IFN-gamma induction by exogenous IL 2 and the inhibitory action of anti-Tac on IFN-gamma production were also seen in cultures of irradiated (2000 R) cells. Treatment of cells with subinducing doses of Con A or phorbol myristate acetate increased IFN-gamma induction by exogenous IL 2. Taken together, the data suggest that endogenously generated IL 2 is a major mediator of IFN-gamma induction in PBL cultures stimulated with antigens or T cell mitogens.