bluuebunny/crossref_metadata_2025_split huggingface dataset:
The modeled structure of the IgG Gar VL region and its implications for anti-flavin and anti-DNP fine specificities.
Authors: Kiefer C R , McGuire B S , Osserman E F , Garver F A 
Published: December 2022

Abstract
The variable domain (V) sequence of the lambda-light chain of the Gar IgG2 human myeloma protein was determined from enzymatically generated peptides that were isolated, characterized, and ordered by overlap and/or by subgroup homology. The sequence consisted of the amino terminal 107 residues of the light chain, and shared subgroup V lambda III-specific residues as well as a pattern of CDR deletions unique to most V lambda III sequences. The structural role of the light V region in the high affinity for flavins and the low affinity for 2,4-dinitrophenyl haptens characteristic of the intact IgG molecule was coarsely assessed by way of model building and by comparison with the refined combining site model of MOPC 315, an Ig with relative affinity values for DNP and riboflavin the converse of those observed in Gar.
Activation of C1 by soluble IgG aggregates as detected by a novel one-step hemolytic assay that specifically measures the proenzyme form of C1s.
Authors: Doekes G , van Es L A , Daha M R 
Published: December 2022

Abstract
A new hemolytic assay is described that specifically measures the precursor form of the C1s subcomponent of the complement system. The assay employs a C1s-depleted reagent obtained by immunoadsorption of fresh human plasma on immobilized goat anti-human C1s antibodies. Linear Z plots are obtained with nanogram levels of precursor C1s, whereas C1s completely fails to induce hemolysis in the assay. Because low concentrations of C1s do not interfere with the activity of precursor C1s, the assay can be used for the stoichiometric measurement of C1 activation. The precursor C1s assay was applied to the study of C1 binding and activation by soluble aggregates of human IgG (AIgG). Incubation of purified human C1 with AIgG caused a temperature-independent consumption of whole C1 hemolytic activity, indicating binding of C1, but almost no consumption of the total (precursor + activated) C1s activity. On the other hand, activation of C1, measured as the time- and temperature-dependent consumption of precursor C1s, could greatly exceed the binding of C1. These findings can be explained by using recent findings concerning the association-dissociation equilibrium between C1q and the tetrameric complex of C1r and C1s.
Analysis of the effect of mast cell granules on lymphocyte blastogenesis in the absence and presence of mitogens: identification of heparin as a granule-associated suppressor factor.
Authors: Frieri M , Metcalfe D D 
Published: December 2022

Abstract
To explore the effect of mast cell products on lymphocytes, the blastogenic response of lymphocytes to mast cell granules in the absence and presence of mitogens was determined. Membrane-free granules (MFG) and dialyzed, washed histamine-free granules (DWG) in the absence of mitogens did not induce significant blastogenesis in peripheral blood mononuclear cells (PBMC) before or after partial depletion of macrophages (5 to 10%). In contrast, concanavalin A- (Con A) (5 micrograms/ml), pokeweed mitogen- (PWM) (1/200 dilution), tetanus toxoid-, and Candida-, but not phytohemagglutinin-, induced blastogenesis in macrophage-depleted PBMC were inhibited by both MFG and DWG. Fractionation of solubilized DWG by anion exchange Dowex chromatography into protein- and heparin-rich fractions revealed the inhibitory activity resided in the heparin-containing fractions. The ability of commercial porcine heparin glycosaminoglycan as well as native rat heparin proteoglycan to inhibit lectin-induced blastogenesis in a dose-response fashion confirmed the previous data with the use of fractionated DWG. Histamine and commercial porcine heparin glycosaminoglycan were not additive in inhibiting lectin-induced lymphocyte blastogenesis. The inhibitory effect of heparin on Con A-induced blastogenesis could be overcome by adding excess Con A to macrophage-depleted mononuclear cell preparations and could be reproduced by using over-sulfated chondroitin 6-sulfate. This is the first examination of the ability of mast cell granules to influence lymphocyte function and the first demonstration of the ability of native heparin proteoglycan to modulate lymphocyte blastogenesis.
Modulation of the biologic activities of IgE-binding factor. IV. Identification of glycosylation-enhancing factor as a kallikrein-like enzyme.
Authors: Iwata M , Munoz J J , Ishizaka K 
Published: December 2022

Abstract
Stimulation of normal rat splenic T cells with pertussigen (lymphocytosis-promoting factor, LPF, from Bordetella pertussis) resulted in the release of a soluble factor that enhanced the glycosylation of IgE-binding factors during their biosynthesis. The soluble factor was detected by the ability of a culture filtrate of LPF-stimulated spleen cells to switch a T cell hybridoma, 23A4, from the formation of unglycosylated IgE-binding factor to the formation of glycosylated IgE-binding factor. The glycosylation-enhancing factor (GEF) had affinity for D-galactose, and the binding of the factor to hybridoma cells via a cell surface galactose was essential for modulation of IgE-binding factors. The GEF was inactivated by irreversible inhibitors of serine proteases such as phenylmethylsulfonyl fluoride, diisopropylfluorophosphate, and p-nitrophenyl ethylpentylphosphonate but was not affected by nonphosphorylating analogues of the organophosphorus compounds. Benzamidine, a competitive and reversible inhibitor of trypsin, also inhibited the glycosylation of IgE-binding factors by GEF. The factor could be purified by absorption to p-aminobenzamidine agarose followed by elution with benzamidine. The capacity of GEF to enhance the glycosylation of IgE-binding factors was inhibited by synthetic substrates of trypsin but not by substrates of chymotrypsin, indicating that GEF is a trypsin-like enzyme. Indeed, trypsin, plasmin, and kallikrein enhanced the glycosylation of IgE-binding factors during their biosynthesis. An inhibitor of trypsin-like enzyme(s), N-alpha-p-tosyl-L-lysine chloromethylketone (TLCK), inhibited trypsin and plasmin but not kallikrein, and TLCK failed to inhibit the GEF-mediated enhancement of glycosylation. It was also found that bradykinin, the biologically active product of cleavage of kininogen by kallikrein, enhanced the glycosylation of IgE-binding factors. The results indicate that GEF is a kallikrein-like enzyme.
Monoclonal anti-parasite and anti-RBC antibodies produced by stable EBV-transformed B cell lines from malaria patients.
Authors: Lundgren K , Wahlgren M , Troye-Blomberg M , Berzins K , Perlmann H , Perlmann P 
Published: December 2022

Abstract
To produce human monoclonal antibodies associated with infectious disease, peripheral blood lymphocytes (PBL) from patients with Plasmodium falciparum malaria were transformed with EB-virus in vitro. To enrich for malaria-specific B cells, PBL were incubated for 3 days with unsoluble P. falciparum antigen before EBV-transformation. Furthermore, cyclosporin A was added during and after transformation to eliminate T cell suppression of B cell growth. Microcultures were screened for antibodies against blood stage antigens of P. falciparum or of noninfected erythrocytes by ELISA and indirect immunofluorescence. Cultures producing anti-P. falciparum and/or anti-erythrocyte antibodies were developed from the lymphocytes of eight patients, including some individuals with their first infection. Positive cultures were cloned and propagated for several weeks. Seven of 15 clones producing antibody at a stable rate have now been kept in cultures for more than 1 yr. Of six cultures analyzed in detail, all produced IgM antibodies of either K or lambda isotype. Although three clones were monoclonal after one cloning, three were oligoclonal. Of the former, two produced P. falciparum-specific antibodies directed to an antigen associated with the surface of merozoites. One of the oligoclonal cultures produced anti-erythrocyte antibodies, and it was probably reacting with spectrin.
Secondary in vitro generation of CTL specific for MM antigen by stimulation with somatic tumor hybrid, but not with parental tumor cells.
Authors: Ishikawa S , Tachibana T 
Published: December 2022

Abstract
Somatic tumor hybrid cells (L-FM3A#2), obtained by hybridization of MM tumor cells (FM3A/R) with HGPRT-less L cells, could induce CTL directed against MM antigen, a tumor-associated transplantation antigen that is expressed on some ascitic mammary tumor cell lines of C3H/He mice; parental tumor cells (FM3A/R) could not produce such CTL in syngeneic mice. In this study, the mechanisms of the generation of CTL by stimulation with L-FM3A#2 hybrid cells were investigated. In the secondary in vitro stimulation system, L cell component(s) that were introduced into hybrid cells by cell fusion play a role in the induction of CTL, as shown by the fact that stimulation with a mixture of L and FM3A/R cells could induce MM antigen-specific CTL, and that the killer helper effect of L cells could be replaced by cell free culture supernatants obtained from co-cultures of unprimed C3H spleen and L cells. IFN activity, but no IL 2 activity, was detected in the culture supernatants. Both IFN and killer helper activity were lost with pH 2 treatment; furthermore, CTL were generated by stimulation of primed spleen cells with FM3A/R cells in the presence of mouse beta-IFN, but not in its absence. These results suggest that IFN liberated by the helper cells that recognize L cell component(s) on the surfaces of tumor hybrid cells plays an essential role in the generation of CTL specific for MM antigen.
The use of specific helper T cell clones to study the regulation of isotype expression by antigen-stimulated B cell clones.
Authors: Teale J M 
Published: December 2022

Abstract
In order to determine the mechanism by which helper T cells regulate the production of the various immunoglobulin (Ig) classes, a number of helper T cell clones specific for keyhole limpet hemocyanin (KLH) were generated. These helper T cell clones then were used in a modified splenic fragment system whereby cloned helper T cells and a source of B cells were limit-diluted into naive, lethally irradiated recipients. The B cell clones that were subsequently stimulated in such an assay system by the addition of the antigen 2,4-dinitrophenol (DNP)-KLH then were tested for the various isotypes produced. The results of these studies indicate that the use of a single helper T cell clone could result in the production of all known Ig isotypes including IgE. Moreover, the use of a single helper T cell clone could result in multiple isotype production by a single B cell clone. However, a comparison of the isotypes secreted by a number of different B cell clones that were stimulated with the same helper T cell clone indicated that a variety of isotypic patterns could be obtained. In addition, it was found that the majority of B cell clones produced in the presence of T cell clones secrete fewer numbers of different isotypes compared with B cell clones generated with a heterogeneous population of T cells. Finally, no evidence could be found for isotype-specific helper T cell clones, although a few of the T cell clones appeared to induce a somewhat restricted isotype pattern in which only two or three different isotypes were observed.
Regulation of the hapten-specific T cell response. I. Preferential induction of hyporesponsiveness to the D-end of the major histocompatibility complex in the hapten-specific cytotoxic T cell response.
Authors: Scott C F , Tsurufuji M , Benacerraf B , Sy M S 
Published: December 2022

Abstract
In this paper we have examined the phenomenon of hapten-specific tolerance in the cytolytic T lymphocyte (CTL), using the trinitrophenyl (TNP) and azobenzenearsonate haptens. We found that the H-2 K and H-2 D-end restricted CTL in H-2a mice are differentiable in the ease with which they are tolerized to the TNP hapten. With TNP modified syngeneic spleen cells (TNP-SC), or low amounts of trinitrobenzylsulfonic acid as tolerogen, preferential hyporesponsiveness of D-end restricted CTL can be observed. Larger doses of hapten, e.g. a higher amount of trinitrobenzylsulfonic acid, will tolerize both K- and D-end restricted TNP-specific CTL in H-2a mice. The phenomenon of preferential D-end restricted CTL hyporesponsiveness is not observed in H-2d, H-2k, or H-2b mice, nor is it observed in H-2a mice with respect to the azobenzenearsonate hapten. We have also shown that the clones of CTL responsible for lysis of TNP-modified allogeneic targets (cross-reactive lysis) in H-2a mice probably overlap with the D-end restricted TNP-specific CTL since D-end restricted hyporesponsiveness induced by intravenous injection of TNP spleen cells also results in the elimination of cross-reactive lysis of TNP-modified allogeneic targets. The possible mechanisms of preferential D-end hyporesponsiveness to the TNP hapten in the H-2a mice as well as its significance and relationship to previous work in this area are discussed in this paper.
Lymphokine-mediated activation of a T cell-dependent IgA antipolysaccharide response.
Authors: Kagnoff M F , Arner L S , Swain S L 
Published: December 2022

Abstract
Immune responses to bacterial polysaccharides are important to host immunity at mucosal surfaces. We previously showed that BALB/c mice produce substantial T cell-dependent IgA responses to alpha (1,3) glucan determinants on the bacterial capsular polysaccharide dextran B1355. The data in this study demonstrate that the requirement for T cells for the activation of the IgA anti-alpha (1,3) dextran B1355 response can be replaced by T cell-derived nonantigen specific helper factors that appear to act during the late stages of B cell differentiation. Supernatants from the activated T cell lines cr-15 and (DL)C.C3.11.75, which contain interferon and late-acting T cell replacing factor activity, supported terminal differentiation of dextran-stimulated B cells to IgA anti-alpha (1,3) glucan antibody-forming cells and substantially increased IgM anti-alpha (1,3) glucan responses in culture. Although supernatants with interleukin 2 activity did not support optimal antigen-driven plaque-forming cell responses, they synergized with supernatants having interferon and T cell replacing factor activity in the production of IgA and IgM anti-alpha (1,3) glucan responses and IgM anti-SRBC responses. Supernatants from the T cell lines B6.11 and (DL)A.4 contained B cell growth factor activity but did not support activation of IgA anti-alpha (1,3) glucan PFC. These studies suggest that interferon and/or T cell replacing factor play an important role in the antigen-driven differentiation of B cells of the IgA and IgM isotypes to antibody-forming cells.
Genetic analysis of the inheritance of B cell hyperactivity in relation to the development of autoantibodies and glomerulonephritis in NZB x SWR crosses.
Authors: Eastcott J W , Schwartz R S , Datta S K 
Published: December 2022

Abstract
Autoimmune NZB mice have a primary B cell abnormality manifested by spontaneous hypersecretion of IgM in short-term cultures. The purpose of this study was to characterize the genes that specify this intrinsic B cell defect and determine their relationship to "autoimmunity" genes. The increase in IgM secretion was shown to result from two independently segregating genetic traits: a) an increased number of IgM-containing cells, and b) an increased rate of secretion of IgM per cell. In this study, approximately 600 NZB, SWR, F1, F2, and reciprocal back-cross mice were hemisplenectomized at 5 to 6 months of age to determine the number of IgM-containing cells and the secretion of IgM in 4-hr cultures. These animals were followed prospectively for the development of anti-DNA (native and denatured) and anti-red blood cell autoantibodies, and proteinuria, and studied at autopsy for the development of glomerulonephritis. The severity and incidence of renal lesions was influenced to some extent by the presence of B cell hyperactivity. However, a proportion of F2 and backcross progeny mice that did not show B cell hyperactivity eventually developed autoantibodies and autoimmune disease.
Relationship of germinal centers in lymphoid tissue to immunologic memory. VI. Transfer of B cell memory with lymph node cells fractionated according to their receptors for peanut agglutinin.
Authors: Coico R F , Bhogal B S , Thorbecke G J 
Published: December 2022

Abstract
We isolated germinal center B cells by exploiting their high affinity for peanut agglutinin (PNA). The PNA+ and PNA- B cells, fractionated by panning on PNA-coated petri dishes, were examined for their ability to transfer memory responses to irradiated recipients at various times after priming. With such fractionated B cells from lymph nodes taken at the peak of germinal center formation, the largest response was obtained in recipients of the PNA+ B cell population. At 4 to 5 wk after priming, and 10 days after challenge with an unrelated antigen, memory responses were approximately equal in recipients of PNA+ or PNA- B cells. At 14 wk after priming, memory responses were found only in recipients of the PNA- B cell population. Memory B cells from the spleen, taken from mice primed in the footpad 8 wk earlier, were also PNA-. Finally, we show that boosting with a TNP-conjugate in the footpad, 6 mo after priming in the same footpad, induced the reappearance of marked memory responsiveness in the PNA+ B cell fraction of the draining node.
A new mediator (suppressor cell induction factor) activating T cell-mediated suppression: characterization of suppressor cells, kinetics of their generation, and mechanism of their action.
Authors: Kasakura S , Taguchi M , Murachi T , Uchino H , Hanaoka M 
Published: December 2022

Abstract
Human T cells precultured in MLC supernatant (SIF) could suppress responder cells in MLC. SIF-activated cells expressed suppressor effects equally on both autologous and allogeneic responder cells in MLC. The suppression observed was not due to cell crowding, cell death, depletion of nutrients, absorption of IL 2, alternation in the kinetics of MLC response, production of soluble inhibitory factor, or generation of cytotoxic cells. In this system, suppressor cells were generated after 5 days of culture, and Ia-positive cells were required in the induction of suppressor cells. Suppressor cells themselves, however, were characterized as Ia-negative subsets of T cells; they could be derived from both Fc-IgG receptor-positive and -negative subsets of T cells. Suppressor activity of SIF-treated cells on the MLC response was sensitive to mitomycin C treatment. They apparently exerted their suppressor effect on some early phase of the MLC response. This early event was almost complete within 48 hr after the initiation of MLC. The possibility that SIF may be involved in T-T interactions required in the generation of effective suppression is discussed.
NK cell function in severe combined immunodeficiency (SCID): evidence of a common T and NK cell defect in some but not all SCID patients.
Authors: Peter H H , Friedrich W , Dopfer R , Müller W , Kortmann C , Pichler W J , Heinz F , Rieger C H 
Published: December 2022

Abstract
The immunologic work-up of eight infants with the clinical diagnosis of severe combined immunodeficiency (SCID) was performed with special emphasis on natural killer (NK) cell function and ontogeny. Contrary to previous reports, our study shows that not all SCID patients lack NK activity; some may even express very high NK- and antibody-dependent cellular cytotoxicity (ADCC). The present group of eight SCID infants was homogeneous with respect to normal levels of the purine metabolism enzymes adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP). They all had low serum Ig levels and were defective for specific antibody formation against BSA and diphtheria toxin (DiT). None of the infants' peripheral blood mononuclear cells (PBMC) proliferated significantly upon in vitro stimulation with PHA, concanavalin A (Con A), pokeweed mitogen (PWM), and irradiated allogeneic lymphocytes. Seven of eight patients, however, responded significantly to mitogenic factors present in a lectin-free interleukin 2 (IL 2) preparation, and two exhibited a positive costimulation as well with simultaneous exposure to IL 2 + Con A. The lymphocyte marker analysis revealed high percentages of OKT10+ cells in seven of eight infants, whereas peripheral T cells (OKT3+) with suppressor/killer (OKT8+) or helper/inducer (OKT4+) phenotypes were abnormally low in all infants with one exception. The PBMC of two patients formed low to normal percentages of E rosettes but expressed no B cell markers (B-/SCID). The six other infants had high percentages of B cells (B+/SCID) but lacked E rosette-forming cells. High NK and ADCC activity was found in the two B-/SCID patients. The B+/SCID infants either totally lacked NK and ADCC function (four of six) or expressed low to normal NK activity together with some T cell markers as revealed by monoclonal antibody staining but not by E rosette formation (two of six). From the data presented, an ontogenic model is proposed that assumes the status of an independent cell lineage in between T cells and monocytes for human NK cells, or that places these cells in close proximity to early differentiation steps of the T cell lineage. In any case, NK cell function clearly constitutes an additional parameter of heterogeneity in the immunologic analysis of SCID.
OKT8 antibody inhibits OKT3-induced IL 2 production and proliferation in OKT8+ cells.
Authors: Welte K , Platzer E , Wang C Y , Rinnooy Kan E A , Moore M A , Mertelsmann R 
Published: December 2022

Abstract
We studied IL 2 production and proliferation induced by OKT3 mitogenic monoclonal antibody in the OKT8+ T cell subset. OKT3 antibody induced IL 2 production and proliferation in OKT8+ cells in a typical time-dependent manner: maximal IL 2 levels were found in 24 hr culture supernatants; maximal proliferation was found on day 3. OKT3 antibody was mitogenic over a wide range of concentrations (0.125 to 500 ng/ml). The presence of OKT8 antibody (greater than or equal to 100 ng/ml) in these cultures resulted in almost complete inhibition of IL 2 production and proliferation. Kinetic studies demonstrate that OKT8 antibody suppresses both IL 2 production and response to exogenous IL 2 in OKT8+ cells when added within the first 2 hr of culture. After 14 to 20 hr of culture, addition of OKT8 only blocks IL 2 production but not the IL 2 response of activated OKT8+ cells. The specificity of inhibition by OKT8 antibody of OKT3 mitogenicity on OKT8+ cells was confirmed by the failure of Leu-I and OKT4 antibody to produce the same effect and by the lack of inhibition by OKT8 antibody of OKT3-induced IL 2 production and proliferation in OKT4+ cells.