bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preferential association of kappa IIIb light chains with monoclonal human IgM kappa autoantibodies.
Authors: Ledford D K , Goñi F , Pizzolato M , Franklin E C , Solomon A , Frangione B 
Published: December 2022

Abstract
The predominance of the relatively uncommon V region subgroup isotype kappa III among the light chains of human monoclonal (IgM kappa) anti-IgG antibodies, (i.e., rheumatoid factors), was further documented through sequence analyses of ten such autoantibodies isolated from IgM-anti-IgG cold-insoluble immune complexes (mixed cryoglobulins). The amino-terminal sequence of all ten kappa-chains was characteristic for kappa III proteins and virtually identical to that of a prototype kappa III light chain. Similar sequence identity was found for kappa-chains isolated from three IgM kappa autoantibodies that formed cold-insoluble immune complexes with low-density lipoprotein (LDL). The thirteen light chains were found to be virtually identical in sequence for the first framework region (FR); ten of these proteins sequenced through the first complementarity-determining region (CDR) and into the second FR were markedly similar. The second CDR of five proteins was almost identical in sequence to that of the prototype kappa III-chain. Concordance was also demonstrated between the structural classification of the light chains as kappa III and their immunochemical classification as members of this V region subgroup. Serologic analyses of light chains isolated from seven IgM kappa autoantibodies (six anti-IgG, one anti-LDL) and of one intact IgM kappa anti-LDL antibody showed that each had antigenic determinants common to kappa II proteins. These light chains also expressed the antigenic determinant(s) of a V-region sub-subgroup of kappa III proteins designated kappa IIIb. Our studies confirm the preferential association of kappa III (and kappa IIIb) light chains with IgM kappa anti-IgG antibodies and demonstrate a similar association for IgM kappa anti-LDL antibodies. The finding that these and other types of IgM kappa autoantibodies, e.g., cold agglutinins, have remarkably similar light chains suggests an inherent restriction in the immune response to self-antigens.
Syngeneic anti-idiotypes against monoclonal anti-HLA-DR antibodies: characterization of recurrent idiotopes.
Authors: Piatier-Tonneau D , Boyer B , Debre P , Charron D J 
Published: December 2022

Abstract
Monoclonal anti-HLA-DR antibody (anti-DR mAb) reactivity was investigated at the idiotypic level; three syngeneic anti-idiotype (Id) sera were raised against three monomorphic anti-DR mAb (206, BM 50, and D 1.12). The syngeneic anti-Id responses exhibited some differences in their intensity and the idiotypic determinants recognized by the three anti-Id sera were localized, at least in part, on the antigen combining site of the respective anti-DR mAb. Idiotype analysis of 24 anti-DR mAb was performed with these anti-Id sera by Id-binding inhibition assays. Idiotypic cross-reactivity was demonstrated for 12 out of the 24 anti-DR mAb, indicating a large degree of idiotypic recurrence. Analysis of the cross-inhibition patterns led us to define at least five sets of recurrent idiotopes: one set cross-reacting with anti-206 Id, the second with both anti-BM 50 and anti-D 1.12 Id, the third with anti-BM 50 Id only, the fourth with anti-D 1.12 Id only, and a fifth set was shared by D 1.12 and NE 4. Eleven monomorphic anti-DR mAb and one polymorphic anti-DR 3 mAb (16.23) did not cross-react with the three anti-Id sera. These results suggest that the mouse antibody response to monomorphic determinants on human Ia antigens is based on a limited number of recurrent idiotopes. In two cases, recurrent idiotopes could be related to a similar anti-DR mAb fine specificity. These anti-Id provide useful reagents to classify and compare anti-DR mAb.
Variation in the glycosylation of the murine sex-limited protein: comparison with the fourth component of murine complement.
Authors: Karp D R 
Published: December 2022

Abstract
The murine sex-limited protein (Slp) is a hemolytically nonfunctional homologue of the fourth component of complement (C4). Two congenic mouse strains, B10.BUA1 (H-2w16) and B10.KPB128 (H-2w19), which have been previously shown to share a variant form of C4 (Karp et al., J. Biol. Chem., 257: 7330-7335), were examined and found to also produce a variant form of Slp. Slp molecules isolated from the plasma or peritoneal macrophage cultures from these strains have an alpha-chain approximately 2,000 daltons smaller than the alpha-chain of Slp from H-2d or H-2w7 mice as judged by sodium dodecyl sulfate (NaDodSO4)/polyacrylamide gel electrophoresis. Expression of this Slp was constitutive, i.e., not regulated by androgen, and is cis-dominant in F1 hybrid mice. Autolysis of the different relative molecular mass (Mr) alpha-chains at the internal thiolester produced similar Mr amino-terminal fragments and different Mr carboxy-terminal fragments. Deglycosylation of the alpha-chains with trifluoromethanesulfonic acid eliminated most, if not all, the Mr difference. The Mr difference was also manifested by the intracellular precursors of Slp and could be eliminated by endoglycosidase H (endo H) treatment. The number of oligosaccharides on the Slp alpha-chain was deduced by limited endo H treatment of Slp synthesized in the presence of swainsonine, a plant alkaloid that prevents maturation of complex-type oligosaccharides. This method is a simple way to enumerate the complex-type, N-linked oligosaccharides on glycoproteins. The genetic variation in the glycosylation of Slp was compared with the known variation in glycosylation of C4, and a scheme depicting some of the structural differences among these molecules was developed.
Inhibition of mitogen-induced lymphocyte proliferation by ouabain: interference with interleukin 2 production and interleukin 2 action.
Authors: Stoeck M , Northoff H , Resch K 
Published: December 2022

Abstract
Since the discovery of IL 2 it has been possible to dissect the mitogenic activation of T lymphocytes into two steps: first, the production of IL 2; and second, the response of IL 2-dependent T cell blasts to IL 2. We investigated the influence of ouabain, a known inhibitor of T cell activation, on the production of and the response to IL 2 in mouse T lymphocytes. Ouabain dose-dependently inhibited DNA synthesis in Con A activated C57BL/6 spleen cells; inhibition below background levels occurred at a concentration of 5 X 10(-4) mol/liter. The action of IL 2 was assayed on a mouse T cell line, named M 2, derived from C57BL/6 spleen cells and maintained in continuous IL 2-dependent culture for more than 21 mo. Ouabain dose-dependently inhibited the response of these cells to mouse IL 2 with optimal inhibition at 10(-3) mol/liter ouabain. The production of IL 2 by Con A-stimulated C57BL/6 spleen cells was also totally inhibited by 10(-3) mol/liter ouabain; 10(-4) mol/liter ouabain inhibited IL 2 production partially, and 10(-5) mol/liter and 10(-6) mol/liter ouabain had no inhibitory effect. The ouabain-mediated inhibition of IL 2 production and of IL 2 action was not due to a nonspecific toxicity, because the preincubation of spleen cells with 10(-3) mol/liter ouabain for 24 hr did not impair their ability to produce IL 2, nor was the response of M 2 cells to exogenously added IL 2 abrogated by the preincubation of the cells with 10(-3) mol/liter ouabain. The data suggest that ouabain acts on two steps during the induction of T cell activation.
Antigen and MHC restriction specificity of two types of cloned male-specific T cell lines.
Authors: Tomonari K 
Published: December 2022

Abstract
Two types of H-Y antigen-specific cloned T cell lines were established. Clone 2-1 is an IAb restricted proliferating T cell line and clone 10-2 is an H-2Db restricted proliferating and cytotoxic T cell line. Clone 2-1 proliferated in response to H-Y antigen with an IAb restriction in the absence of IL 2. IAb mutant B6.C-H-2bm12 (bm12) mice did not stimulate this clone. This defect may be the cause of the unresponsiveness to H-Y antigen with cytotoxic T lymphocytes (CTL) in bm 12 mice (i.e., the failure of activation of H-Y-specific helper T cells). Although (B10.A X bm12)F1 mice are known to show functional complementation, as demonstrated by the presentation of insulin to helper T cells and the H-Y-specific CTL response, the F1 male cells could not stimulate this clone. The IA determinant restricting H-Y antigen presentation to helper T cells and/or the H-Y antigenic determinant seems to differ between C57BL/6 (B6) and the F1 mice. Monoclonal anti-IAb antibodies but not anti-H-Y antibodies blocked the proliferation of this clone. The clone had no cytotoxic activity unless Con A was added to the cytotoxicity assay culture. Clone 10-2 proliferated in response to H-Y antigen with an H-2Db restriction. Proliferation was not observed unless specific stimulator cells and IL 2 were supplied to the culture; IL 2 alone could not support this clone. The clone did not respond to male cells from the H-2Db mutant B6.C-H-2bm14 (bm14). The clone had cytotoxic activity against male H-2Db+ cells but not against male bm14 cells. This evidence indicates that the mutation of bm14 occurred in the structural gene coding for a molecule on which a determinant restricting the recognition of H-Y antigen by B6 CTL exists. The phenotypes of clone 2-1 were Thy-1.2+, Ly-1.2-, Ly-2.2-, IAb-, and H-2Kb+, and the phenotypes of clone 10-2 were Thy-1.2+, Ly-1.2-, Ly-2.2+, IAb-, and H-2Kb+.
Modulation of B and T cell subsets in mice treated with fractionated total lymphoid irradiation (TLI). IV. Expression of TL4-bearing cells in spleen and bone marrow of TLI-treated mice.
Authors: Zan-Bar I 
Published: December 2022

Abstract
The pre-thymic cell phenotypes arising in spleen and bone marrow (BM) of fractionated total lymphoid irradiation (TLI)-treated mice are characterized in this paper. Different strains of mice received 200 rad lymphoid irradiation daily for 8 to 10 days. At different time intervals after treatment, BM or spleen cells of treated mice were stained with a battery of antisera directed specifically to TL and Thy-1 antigens. Analysis of the stained cells on a fluorescence-activated cell sorter (FACS) apparatus revealed that 10 to 30% of spleen or BM cells of TLI-treated mice were TL+ cells whereas no TL+ cells could be found in the same organs in the normal untreated mice. The appearance of TL+ cells in the spleen and BM of TLI-treated mice was found to be thymic independent, as thymectomy of mice neither prevented nor altered the kinetics of TL+ cell appearance. The sequence of antigenic marker appearance reveals that TL markers precede Thy-1 markers and that TLaa markers precede TL4 antigen. The relevance of the TL4+ cells to the development of leukemias is discussed.
Differential production of deoxyadenosine by human T and B lymphoblasts.
Authors: Iizasa T , Kubota M , Carson D A 
Published: December 2022

Abstract
The association of a genetic deficiency of adenosine deaminase (ADA) with immunodeficiency disease has emphasized the importance of deoxyadenosine and adenosine metabolism for human lymphocyte function. However, information concerning the endogenous production and metabolism of deoxyadenosine and adenosine in normally growing human T and B lymphoblasts is lacking. In the present experiments, we used a diverse series of cell lines deficient in individual enzymes of purine metabolism to quantitate the de novo formation of deoxyadenosine and adenosine in human T lymphoblasts (CEM), B lymphoblasts (WI-L2), and histiocytic lymphoma cells (DHL-9). The B lymphoblasts and histiocytic lymphoma cells generated deoxyadenosine at a rate of 60 to 80 pmol/hr/10(7) cells. This value was several fold greater than the rate of production of deoxyadenosine by T cells (6 to 7 pmol/hr/10(7) cells). Deoxyadenosine synthesis required ribonucleotide reductase activity, and was maximal during the S-phase of the cell cycle. The T and B lymphoblasts formed relatively similar amounts of adenosine (870 to 1620 pmol/hr/10(7) cells) throughout the cell cycle. In ADA-deficient cells, a major fraction of the deoxyadenosine synthesized de novo was excreted into the extracellular space. These results establish that the endogenous synthesis and metabolism of deoxyadenosine (but not adenosine) is distinctly different in T and B lymphoblasts.
Interleukin 2 receptor expression by activated HNK-1+ granular lymphocytes: a requirement for their proliferation.
Authors: Abo T , Miller C A , Balch C M , Cooper M D 
Published: December 2022

Abstract
A subpopulation of HNK-1+ cells was found to express interleukin 2 receptor (IL 2R) as monitored by the anti-Tac monoclonal antibody after lectin or allogeneic cell stimulation. When blood mononuclear cells were stimulated with phytohemagglutinin (PHA) or concanavalin A for 3 days, or with pokeweed mitogen or allogeneic mononuclear cells for 6 days, virtually all of the HNK-1+ cells remained as small resting lymphocytes. One-fourth of these HNK-1+ cells expressed IL 2R, however, usually within 18 hr after stimulation. Neither circulating HNK-1+ cells nor unstimulated HNK-1+ cells in short-term culture expressed IL 2R. Only the subset of HNK-1+ cells that expressed T cell surface markers, such as the sheep erythrocyte receptor and Leu-4 antigen, could be induced to express IL 2R. When long-term cultures of HNK-1+ cells were established with initial PHA stimulation and the continued presence of IL 2, a majority of the cells was found to express the IL 2R. When anti-Tac antibody was added to the long-term cultures, proliferation of the HNK-1+ cells was completely inhibited. These results suggest that entry into growth cycle by this subpopulation of HNK-1+ granular lymphocytes may require two signals: a relatively nonspecific ligand interaction with cell surface glycoprotein(s) to induce expression of IL 2R, and subsequent IL 2 interaction with these specific cell surface receptors.
Preparation of goat antibodies against interleukin 1: use of an immunoadsorbent to purify interleukin 1.
Authors: Mizel S B , Dukovich M , Rothstein J 
Published: December 2022

Abstract
Antibodies with specificity for interleukin 1 (IL 1) were produced in a goat immunized with purified IL 1 alpha obtained from the murine macrophage cell line, P388D1. The anti-IL 1 IgG were capable of completely inhibiting the biologic activity of IL 1 in the murine thymocyte assay but had no effect on IL 2-driven T cell responses. Although the anti-IL 1 IgG were produced by using mouse IL 1, these antibodies also recognized IL 1 prepared from a human monocyte leukemia cell line. An immunoadsorbent column was prepared and used for the large-scale purification of IL 1 in relatively high yield. Approximately 250 micrograms of purified IL 1 were obtained from 50 liters of culture fluid, the yield being 20% of the initial activity. Six major species of IL 1 were resolved by using tris-glycinate discontinuous polyacrylamide gels. The purified IL 1 exhibited 50% of its maximal activity in the thymocyte proliferation assay at a concentration of approximately 1 X 10(-11) M.
Biochemical and physicochemical characterization of mouse B cell growth factor: a lymphokine distinct from interleukin 2.
Authors: Farrar J J , Howard M , Fuller-Farrar J , Paul W E 
Published: December 2022

Abstract
A subline of the C57BL/6 mouse EL-4 thymoma produces upon stimulation with phorbol myristate acetate (PMA) a B cell growth factor (BCGF) that co-stimulates anti-IgM-stimulated splenic B cells. The BCGF present in the EL-4 thymoma culture supernatants is shown to be distinct from IL 2 by a variety of chromatographic criteria. Untreated BCGF exhibits a heterogeneity of isoelectric points (pH 6.4 to 6.6, 7.4 to 7.6, 8.5 to 8.7) all of which are more alkaline than that of IL 2 (pl 3.5 to 4.8). Neuraminidase-treated BCGF exhibits a single major pl of 9.3 that is also distinct from similarly treated IL 2. Moreover, IL 2 and BCGF exhibit distinct monomeric m.w. by SDS gel electrophoresis under nonreducing conditions (IL 2 is 21,000; BCGF is 11,000 and 15,000). The biologic activity of IL 2 is sensitive to trypsin inactivation as is BCGF activity. Thus, BCGF and IL 2 appear to be biologically and biochemically distinct glycoproteins.
Biosynthesis, glycosylation, and in vitro translation of the human T cell antigen Leu-4.
Authors: Bergman Y , Stewart S J , Levy S , Levy R 
Published: December 2022

Abstract
Two families of polypeptides were found in immunoprecipitates formed from human T cell lines by using the monoclonal antibody anti-Leu-4. When analyzed by one- and two-dimensional SDS-PAGE, the first family consisted of members with m.w. of 26,000 and isoelectric points that varied from very basic to acidic. The second family consisted of members with m.w. of 22,000 to 23,000 and isolectric points that varied from neutral to very acidic. The biosynthetic processing and intracellular glycosylation of several of these polypeptides were examined. Some, but not all, intracellular forms of the Leu-4 antigen contained N-linked oligosaccharides of the high mannose type. By using messenger RNA from human T cell lines, intracellular forms of Leu-4 were shown to be accurately translated and properly processed by Xenopus oocytes in vitro.
Regulation of azophenylarsonate-specific repertoire expression. II. Fine specificity and isotype heterogeneity of anti-arsonate antibodies.
Authors: Sigal N H 
Published: December 2022

Abstract
This report investigates the isotope and binding site heterogeneity of IgG anti-azophenylarsonate (ARS) monoclonal antibodies derived from splenic fragment cultures of nonimmune and immune A/J mice. By using five arsanilic acid derivatives in a hapten inhibition assay to determine fine specificity, the secondary ARS-specific repertoire was found to be extremely heterogeneous, with 52 unique patterns among the 81 antibodies analyzed. CRIA+ and CRIA+/- clonotypes were as heterogeneous as CRIA- antibodies, but a majority of CRIA+/- clones maintained a characteristic relative affinity for two of the haptens, p-arsanilic acid (p-ARS) and p-azobenene arsonic acid-N-tyrosine (ABA-tyr), which was identical to the prototype CRIA+ hybridoma protein R16.7. We also observed that the average relative affinity of CRIA- antibodies from immunized donors was higher than nonimmune mice with respect to p-ARS and ABA-tyr, and that there was a further increase in avidity to ABA-tyr over time after immunization. In contrast, no affinity maturation occurred among the CRIA+ and CRIA+/- clones. Rare antibodies were also identified within the nonimmune repertoire that had higher relative affinities than R16.7. Despite this, a greater proportion of CRIA+ and CRIA+/- clones produced IgG antibody in vitro. Thus, the predominance of CRIA+ antibodies in the ARS-specific immune repertoire and the preferential differentiation of CRIA+ precursor cells to IgG secretors cannot be entirely explained by the avidity of this clonotype family for p-ARS or ABA-tyr.
A circular antibody-antigen complex is responsible for increased affinity shown by mixtures of monoclonal antibodies to human chorionic gonadotropin.
Authors: Moyle W R , Anderson D M , Ehrlich P H 
Published: December 2022

Abstract
Mixtures of some pairs of monoclonal antibodies that have separate epitopes on the beta-subunit of hCG have increased affinity for the hormone relative to that of either antibody alone. A mathematical model developed to explain the phenomenon predicted that a circular tetrameric complex composed of each antibody and two molecules of hCG was responsible for the effect. This structure has now been identified experimentally by the following criteria: 1) the m.w. of the complex observed by electrophoresis (370,000 g/mol) and gel filtration (440,000 g/mol) was in agreement with the m.w. expected for a tetramer composed of two molecules of antibody and two molecules of hCG (i.e., 376,000 g/mol); 2) the ratio of individual antibodies to hCG measured with the use of 131I and 125I-labeled antibodies and/or hCG was 1:1:2; and 3) the complex failed to adhere to affinity columns containing either antibodies or hCG covalently coupled to Sepharose. These columns adsorbed B101, B102, hCG, and mixtures of B101 plus hCG or B102 plus hCG. The observations made with the affinity resins are compatible with a circular model for antigen-antibody complex in which the epitopes of the antigen and the binding site of the antibodies were mutually and completely obscured. Although not studied in detail, a similar complex was formed when the beta-subunit of hCG was substituted for the intact hormone. In addition, a mixture of antibodies that bound to the alpha- and beta-subunits of hCG (i.e., A102 and B102) and that had a higher affinity for the hormone than either antibody also gave rise to a similar species that could be detected after electrophoresis. A pair of antibodies that bind to separate epitopes on the beta-subunit (i.e., B101 and B103) and do not show enhanced affinity for hCG failed to form a stable complex that could be identified as a separate species after electrophoresis. Thus, the studies reported here confirm earlier theoretical predictions linking the increase in affinity observed on mixing monoclonal antibodies to the formation of a circular complex.
Differential survival of Leishmania donovani amastigotes in human monocytes.
Authors: Pearson R D , Harcus J L , Roberts D , Donowitz G R 
Published: December 2022

Abstract
Leishmania donovani is an important intracellular protozoal pathogen of man; it is found solely within macrophages in its amastigote stage in humans, and exists in its extracellular, flagellated promastigote stage in the sandfly, its arthropod vector. To determine if either stage of L. donovani was capable of surviving within monocytes--the oxidatively active precursors of tissue macrophages--interactions of the parasite with human monocytes were studied in vitro. Amastigotes and promastigotes were ingested to a comparable degree by monocytes; whereas 79% of promastigotes were killed within 48 hr, however, amastigotes survived and multiplied threefold over 5 days. Promastigotes, which have been shown to be sensitive to hydrogen peroxide-peroxidase-halide microbicidal mechanisms, elicited a phagocytic oxidative burst that was 49% of the response to serum-opsonized zymosan, as assessed by luminol-enhanced chemiluminescence. NBT was reduced to formazan in 71% of monocytes exposed to promastigotes. The death of promastigotes within monocytes could be attributed at least in part to oxidative microbicidal mechanisms because there was no significant decrease in the number of cell-associated parasites in monocytes from donors with chronic granulomatous disease of childhood. In contrast to promastigotes, amastigotes survived within monocytes, despite eliciting an oxidative response that was 27% of the response produced by serum-opsonized zymosan; this response was not significantly different from that produced by promastigotes. In a phagocyte-free system, amastigotes were found to be sevenfold more resistant than were promastigotes to the lethal effects of hydrogen peroxide. The survival of L. donovani in human monocytes is thus dependent on the parasite stage; promastigotes are ingested, they elicit an oxidative burst, and the majority are killed by oxidative microbicidal mechanisms, whereas amastigotes are ingested and survive to parasitize human monocytes successfully, despite eliciting a phagocytic oxidative burst.