bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of early stages of T lymphocyte development in the thymus cortex and medulla.
Authors: Scollay R , Shortman K 
Published: December 2022

Abstract
Thymocyte subpopulations with a phenotype suggesting they are early stages of T cell development in the adult mouse thymus were characterized and isolated by using multiparameter flow cytometry and sorting, in conjunction with selective killing with antibody and complement (C). The intrathymic localization of these subpopulations was assessed by dipping the thymus in fluorescent dyes to selectively label outer-cortical cells. The main phenotypic markers used were sensitivity to C-mediated lysis by the monoclonal antibody B2A2 (which spares most prothymocytes but kills most thymocytes), the expression of the T cell lineage specific markers Ly-2 and L3T4, and the levels of the common T cell antigens Ly-1 and Thy-1. A preliminary selection for cells lacking Ly-2 and L3T4, or resistant to B2A2 and C, produced a population of large cells, only 5% of all thymocytes and distinct from the typical cortical blast cells. This population of putative early thymocytes was itself heterogeneous, consisting of eight subpopulations separable by phenotype and intrathymic localization. One group of two subpopulations (B2A2-, Ly-1++, Thy-1+ and either Ly-2+ L3T4- or Ly-2- L3T4+) appeared to be of medullary location, and their phenotype suggested they could have been early members of the medullary lineages. Another group of two subpopulations (B2A2-, Ly-1++, Thy-1-, Ly-2-, L3T4- and B2A2-, Ly-1++, Thy-1+, Ly-2- L3T4-) did not show a clear localization pattern and may have represented cells in an earlier stage of transition to medullary phenotype and location. A quite different group of three subpopulations (B2A2++, Ly-1-, Thy-1-, Ly-2- L3T4-; B2A2++, Ly-1-, Thy-1+, Ly-2-, L3T4-; and B2A2++, Ly-1+, Thy-1++, Ly-2- L3T4-) was concentrated in the outer cortex and seemed to represent a series of stages of a cortical pathway, before the typical cortical blast cells. Finally, a very minor subset (0.2% of thymocytes), lacking all these markers, was concentrated in the outer cortex; this fifth group had the phenotype expected of the earliest intrathymic precursor cells. The results suggest that the separate developmental streams of cortical and medullary thymocytes may be traced back, via these minor early blast subpopulations, to common precursor cells in the outer cortex.
Enhanced activation of a T cell line specific for acetylcholine receptor (AChR) by using anti-AChR monoclonal antibodies plus receptors.
Authors: Schalke B C , Klinkert W E , Wekerle H , Dwyer D S 
Published: December 2022

Abstract
Immune complex-mediated regulation of the immune response has been studied by using T cell lines and monoclonal antibodies (MAb), both specific for the acetylcholine receptor (AChR). Rat T lymphocytes bearing the W3/25 phenotype and specific for AChR from Torpedo californica have been propagated in vitro for nearly 1 yr. These T cells proliferate in response to optimal concentrations of AChR presented by irradiated syngeneic thymus cells. At suboptimal concentrations of antigen there is little activation of the T cell line. We report here that the addition of small amounts of anti-AChR MAb produces dramatic stimulation of the T cell lines at suboptimal doses of AChR. Enhanced activation depends on the isotype and not the fine specificity of the MAb that are used. The observed phenomenon is antigen specific, and in fact, the immune complexes may actually suppress the proliferative response of irrelevant T cells to some extent. The MAb plus antigen are rapidly bound to the surface of the antigen-presenting cell, which we have shown is the dendritic cell.
Hormonal modulation of responses to thymus-independent and thymus-dependent antigens in autoimmune NZB/W mice.
Authors: Brick J E , Wilson D A , Walker S E 
Published: December 2022

Abstract
Previous work suggested that gonadal steroids influence immunity through the thymus, but the mechanisms were unclear. To investigate the effects of these hormones on immune responses to T1 and TD antigens in autoimmune mice, we studied hybrid NZB/W mice and the nonautoimmune DBA/2 strain. Mice castrated at 14 days of age were implanted with Silastic capsules releasing, in adults, physiologic levels of E2 in males or Te in females. Sham-operated controls received empty capsules. Splenic PFC were quantified 4 to 5 days after challenge with the TI2 antigen TNP-Ficoll, the TI1 antigen TNP-LPS, or the TD antigen SRBC. Young castrated NZB/W males implanted with E2 had striking enhancement of IgM responses to TNP-Ficoll when compared to castrated Te-treated females and comparable sham-operated controls of both sexes. E2 also stimulated responses to TNP-LPS. In response to challenge with SRBC, young E2-treated NZB/W males had a consistent trend to increased IgM PFC, and the stimulatory effect of E2 on IgG plaques was variable. Physiologic doses of Te had no consistent effect on responses in young mice. In old female NZB/W mice, Te caused PFC response after immunization with TNP-Ficoll to resemble age-matched NZB/W males. As sham-operated NZB/W females grew older, PFC responses to SRBC fell. This age-related phenomenon was delayed, however, in female castrates implanted with Te. In contrast, Te clearly suppressed responses to TNP-LPS. Implantation of E2 did not alter responses to TNP-Ficoll, TNP-LPS, or SRBC in nonautoimmune DBA/2 males. This finding suggested that exogenous E2 given in physiologic doses did not influence immunologic responsiveness in a normal strain to the degree seen in hormone-sensitive NZB/W mice. It was concluded that E2 enhanced responses to a variety of exogenous antigens in autoimmune NZB/W mice. The most consistent E2-induced increase in PFC response was observed with TI antigens, suggesting that E2 exerted its effects on B cells or Ts.
Differentiation of murine B cell precursors in agar culture. II. Response of precursor-enriched populations to growth stimuli and demonstration that the clonable pre-B cell assay is limiting for the B cell precursor.
Authors: Paige C J , Skarvall H , Sauter H 
Published: December 2022

Abstract
We established culture conditions under which fetal liver-derived B cell progenitors divide and differentiate in semisolid agar, forming colonies containing antibody-secreting cells. An important feature of this assay system is that, under certain conditions, it is limiting for only one component. This was revealed by determining the slope of the least-squares log-log regression line generated when the initial seeding density was varied. When support for the growth of the clonable pre-B cells was provided by fetal liver-derived adherent accessory cells, the slope of the regression line was 1, consistent with the interpretation that only one component, the pre-B cell, was limiting under these conditions. This interpretation was tested in the present report by positive selection for cells expressing B220, Lyb-2, or AA4.1, surface markers known to be present on cell lines of the B lineage. In all cases, an increased incidence of clonable pre-B cells was observed. Furthermore, regression analysis of titration experiments undertaken with these enriched populations revealed that the assay was still limiting for a single component. A second set of growth conditions have been defined in which the clonable pre-B assay appears to be limiting for more than one component. These conditions are obtained when the adherent accessory cells are replaced by one of three distinct hemopoietic growth factors, including CSF-1 (macrophage growth factor), GM-CSF (neutrophil/macrophage growth factor), or Multi-HGF (multi-lineage hemopoietic growth factor, also called BPA or IL 3). The most straightforward interpretation of these data is that a second cell type, distinct from the B cell precursor and dependent on the growth factors, was limiting under these conditions. In the present report, this hypothesis was confirmed because growth factor responsiveness was completely absent in B220 and Lyb-2-enriched populations. Factor responsiveness was found in unseparated fetal liver and in AA4-enriched populations. However, the AA4-enriched populations, in contrast to the B220- or Lyb-2-enriched populations, also contained a large number of factor-responsive neutrophil/macrophage colonies, raising the possibility that the effect of factors on AA4+ clonable pre-B cells was accessory cell-mediated.
Distribution of cells bearing the Tac antigen during ontogeny of human lymphoid tissue.
Authors: Hofman F M , Modlin R L , Bhoopat L , Taylor C R 
Published: December 2022

Abstract
The monoclonal antibody anti-Tac, which binds to the interleukin 2 (IL 2) receptor, was used to identify this antigen in human fetal and adult lymphoid tissue. Liver, spleen, thymus, lymph node, and peripheral blood were examined for Tac-positive cells with the use of frozen sections or cytocentrifuge preparations. The results show that cells in the fetal and neonatal thymus express the Tac antigen; these cells are predominantly located in the medulla. The liver and spleen of both fetus and adult exhibit very few Tac-positive cells. Double staining demonstrates that cells bearing the Tac-antigen stain with Leu-4, an anti-T cell antibody. In adult lymph node tissue, the Tac-bearing cells are predominantly distributed in the interfollicular area, with positive cells also present in the germinal center and mantle zone. The Tac antigen is present on both T and B cells. Few Tac-positive cells are present in the circulating peripheral blood.
Analysis of triiodothyronine and thyroxine-binding autoantibodies in chickens susceptible to autoimmune thyroiditis.
Authors: Brown T R , Bagchi N , Sundick R S 
Published: December 2022

Abstract
This report reveals a surprisingly high incidence of thyroid hormone (T3 and T4) autoantibodies (THA) and thyroglobulin autoantibodies in a closed flock of untreated Cornell strain (CS) White Leghorn chickens. This flock is closely related to the Obese strain chicken, which develops a severe spontaneous autoimmune thyroiditis. A sensitive electrophoretic autoradiographic assay for THA was developed. This assay was applied to the study of autoantibodies to T3 and T4 in the sera of adult female CS chickens. Of 109 females, 29.4% had antibodies to T3 and 18.4% had antibodies to T4. The incidence of thyroglobulin antibodies, determined by passive hemagglutination, was 15.6%. The presence of THA affected RIA measurements because serum T3 and T4 hormone concentrations appeared elevated in those birds with moderate to high antibody levels. There was major variance in the electrophoretic heterogeneity of the THA from individual chickens; i.e., some of the sera contained antibodies to T3 or T4 that appeared to be monoclonal, whereas other sera exhibited polyclonal multi-banded patterns. To determine if antibodies reactive with T3 and T4 (which are haptens) were generated by antibody responses to the T3/T4 sites on the thyroglobulin molecule, competitive binding assays were performed to determine the relative binding affinities of the antibodies for the haptens (T3/T4) and the "hapten-conjugate" (thyroglobulin). In these assays, thyroglobulin competed with the haptens, thus supporting the above hypothesis.
Interleukin 2 (IL 2) administered in vivo: influence of IL 2 route and timing on T cell growth.
Authors: Cheever M A , Thompson J A , Kern D E , Greenberg P D 
Published: December 2022

Abstract
The influence of the route and the frequency of IL 2 administration on the ability of IL 2 to induce the growth of activated T cells in vivo was evaluated. Initial pharmacokinetic studies confirmed that i.v. injection of IL 2 results in a relatively high peak serum concentration, but a short serum half-life. By contrast, i.p. or subcutaneous (s.c.) injection of IL 2 results in a lower peak concentration but a prolonged serum half-life. The bioavailability of IL 2 administered by these routes was assessed by measuring the in vivo growth of adoptively transferred T cells that had been previously cultured long-term with IL 2, because the growth of such cells in vivo has been shown to be proportional to the dose of IL 2 administered. The results demonstrated that i.p., s.c., or i.v. administration of IL 2 each resulted in marked donor T cell growth in vivo. Thus, IL 2 can function in vivo at sites distant to the sites of injection. In addition, the magnitude of T cell growth in vivo varied dependent on the route of IL 2 administration and correlated with the length of time IL 2 was detectable in serum, rather than the peak level achieved (i.e., IL 2 inoculated i.v. had the highest peak concentration but was least effective). As suggested by these findings, dividing the total dose of IL 2 into frequent low-dose injections was more effective in inducing T cell growth in vivo than was dividing the total dose of IL 2 into less frequent higher-dose injections. These studies confirm the great potential for IL 2 to induce the growth of activated of T cells in vivo and demonstrate that the rate of T cell growth reflects not only the dose but also the route and timing of IL 2 administration.
Role of BCGFII in the differentiation to antibody secretion normal and tumor B cells.
Authors: Swain S L 
Published: December 2022

Abstract
This report describes the effects of B cell growth factor (BCGFII) and other lymphokines in the differentiation of normal and tumor B cells. We compared BCL1 tumor B cells, normal B cells giving rise to a polyclonal response without the intentional addition of antigen, and an antigen-driven, SRBC-specific response. BCL1 tumor B cells gave maximum PFC responses when partially purified BCGFII was added or when suboptimal doses of BCGFII were mixed with one of several putative terminal differentiation factors we call B cell differentiation factors BCDF. IFN-gamma was not active as any of these factors. Maximum polyclonal responses of B cells were seen when either IL 2 or BCGFII were mixed with BCDF. In contrast, SRBC-specific responses showed a strict requirement for IL 2, and BCGFII and BCDF synergized with IL 2 to give a maximum response. The involvement of BCGFII in all of these responses suggests that BCGFII acts as a growth factor for a population of B cells that has differentiated much of the way towards Ig secretion, and that many B cells become responsive to this growth factor. In addition, the fact that different lymphokine requirements were seen in the different experimental systems raises the possibility that there are multiple pathways to Ig secretion, and suggests that different subpopulations of B cells defined either by different lineages or by different stages of development within a single lineage have requirements for distinct lymphokines that regulate their growth and differentiation.
Monoclonal antibody BA-1 recognizes a novel human leukocyte cell surface sialoglycoprotein complex.
Authors: Pirruccello S J , LeBien T W 
Published: December 2022

Abstract
With the use of the monoclonal antibody BA-1, we have identified and characterized a unique molecular complex on the surface of human B lymphocytes. Despite the marked pronase sensitivity of the BA-1 antigen/epitope on the cell surface, repeated attempts to surface or biosynthetically radiolabel the antigen by using standard protein labeling techniques were unsuccessful. The antigen was identified by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis after radiolabeling carbohydrate residues. Surface labeling of galactosyl residues by the neuraminidase/galactose oxidase/3HNaBH4 method revealed a three chain, nondisulfide-linked glycoprotein complex of 45, 55, and 65 kilodaltons (kDa), which we have designated gp45/55/65. Under nonreducing gel conditions there were shifts in the mobility of the 55- and 65-kDa components, consistent with the presence of intrachain disulfide linkages. Surface labeling of sialic acid residues by the sodium periodate/3HNaBH4 method revealed the presence of sialic acid residues on the 45- and 55-kDa components. Two-dimensional gel analysis indicated that the 55-kDa component had an acidic pI of approximately 4.0 and considerable charge heterogeneity, most likely attributable to sialic acid. In contrast, the 45-kDa component had a neutral pI of approximately 7.5. Despite the difficulty in radiolabeling amino acids in gp45/55/65, digestion with V8 protease and pronase clearly demonstrated the presence of protein cores in all three components. Consonant with prior serologic studies with the use of BA-1, we could identify gp45/55/65 on B lymphocytes, B cell precursor acute lymphoblastic leukemias, neutrophils, and eosinophils. This molecular complex has, to our knowledge, not been heretofore described on human B cells and is quite novel in its structure and labeling properties.
Identification of a human granulocyte functional antigen (GFA-2) involved in antibody-dependent cell-mediated cytotoxicity and phagocytosis.
Authors: López A F , Begley G , Andrews P , Butterworth A E , Vadas M A 
Published: December 2022

Abstract
A human neutrophil- and eosinophil-specific surface antigen, GFA-2, has been found to be involved in the antibody-dependent cell-mediated cytotoxicity (ADCC) to extracellular targets, and in phagocytosis. The monoclonal antibody (MAb) WEM-G11 was produced which recognizes the GFA-2 structure. This MAb, when used as F(ab')2, stimulated human neutrophils to kill antibody-coated P815 cells and, in the case of human eosinophils, increased their cytotoxic effect on schistosomula of Schistosoma mansoni in a dose-dependent manner. MAb WEM-G11 F(ab')2 also stimulated the phagocytosis of antibody-coated sheep erythrocytes by neutrophils. The effect of WEM-G11 F(ab')2 was specific, because other MAb, whether tested in the form of F(ab')2 fragments or as whole IgG, failed to stimulate neutrophils despite binding to these cells. In contrast to the F(ab')2 fragments of these cells. In contrast to the F(ab')2 fragments of WEM-G11, the whole IgG of this MAb inhibited ADCC and phagocytosis, presumably through interaction with granulocyte Fc receptors. WEM-G11 F(ab')2, and to a greater extent WEM-G11 IgG, induced degranulation, but only from cytochalasin B-treated neutrophils. GFA-2 was absent from lymphocytes, monocytes, erythrocytes, and myeloid and erythroid colony-forming cells, as shown by flow cytometry and colony-forming experiments. GFA-2 appeared at the promyelocytic stage and increased in density as neutrophils became more mature. In the mature neutrophil, the number of binding sites for WEM-G11 were found to be about 20,000 per cell. By immunoprecipitation, it appeared that GFA-2 consisted of a polypeptide chain of about 95,000 m.w. and a low m.w. peptide of about 43,000. By immunoblotting, it was demonstrated that the epitope recognized by WEM-G11 is in the chain of m.w. 95,000. GFA-2 thus constitutes a novel human granulocyte-specific antigen that is central to the functional activity and differentiation of these cells.
Functional studies on the role of I-A molecules expressed by the antigen-specific T suppressor cell clone HF1.
Authors: Heuer J , Kölsch E 
Published: December 2022

Abstract
The antigen-specific T suppressor (Ts) cell clone HF1 (Thy-1.2+, I-Ak+, I-Ek+) was isolated from a CBA/J mouse tolerized to low doses of bovine serum albumin (BSA), and a subclone was adapted to grow in the absence of antigen-presenting cells. The functional role of the I-Ak molecules endogenously expressed by HF1 Ts cells was analyzed by using anti-I-Ak monoclonal antibodies (mAb) in attempts to block the antigen-induced proliferation of these cells. Among a panel of anti-I-Ak mAb tested, only the H118-49 mAb directed against the private determinant Ia.m1 blocked BSA-induced proliferation. The data presented here suggest a selective regulatory role of membrane-bound I-Ak molecules in the antigen-induced signal transmission.
p65: A C3b-binding protein on murine cells that shares antigenic determinants with the human C3b receptor (CR1) and is distinct from murine C3b receptor.
Authors: Wong W W , Fearon D T 
Published: December 2022

Abstract
Affinity-purified rabbit antibody to the human C3b receptor (CR1) cross-reacted with an antigen that was expressed on murine splenocytes, lymph node cells, thymocytes, peritoneal macrophages, erythrocytes, and L929 cells, as assessed by flow cytofluorographic analysis of indirectly stained cells. The cell surface antigen recognized by antihuman CR1 had a Mr of 60,000 to 65,000 on each cell type, and the cross-reactive epitope(s) was sensitive to reduction with dithiothreitol but not to oxidation with NaIO4. Analysis by affinity chromatography of murine splenic B lymphocytes identified two cell surface proteins capable of binding to guinea pig C3b (C3bgp). The larger polypeptide had a Mr of 210,000, was not present in L929 cells, and may represent the murine CR1. The smaller polypeptide of 65,000 Mr was also present on L929 cells and was shown to constitute the cross-reactive antigen. Adsorption of detergent lysates of L929 cells with C3bgp-Sepharose depleted by 44% the antigen recognized by anti-human CR1; the C3bgp-binding protein and the cross-reactive antigen exhibited similar patterns on two-dimensional gel electrophoresis; and the isolated C3b-binding protein could be immunoprecipitated with anti-human CR1. Thus, the murine cell surface protein, termed p65, that is antigenically cross-reactive with human CR1 shares a capacity for binding to C3b in its detergent-solubilized form but is distinct from murine CR1 in its lower Mr, wider cellular distribution, and inability to mediate the adherence of C3b-coated particles in its native, membrane-associated form.
Osmotic stress and the freeze-thaw cycle cause shedding of Fc and C3b receptors by human polymorphonuclear leukocytes.
Authors: Takahashi T , Inada S , Pommier C G , O'Shea J J , Brown E J 
Published: December 2022

Abstract
A major problem in the cryopreservation of human polymorphonuclear leukocytes (PMN) is the loss of phagocytic function in cryopreserved cells. This is not a problem with cryopreserved monocytes. To study the reasons for this difference in detail, PMN and monocytes were either osmotically stressed in hypertonic media or were frozen to various temperatures. Cells were then returned to conditions of physiologic osmolarity and temperature. All cells remained viable. However, the ability of PMN to phagocytize bacteria and to bind sheep erythrocytes (E) opsonized with IgG, C3b, or C3bi decreased sharply after exposure to media of 600 mOsM or greater and after freezing to -1.5 degrees C. In contrast, monocytes were unaffected until a concentration of 1500 mOsM or a freezing temperature of -5 degrees C was exceeded. To determine whether the functional losses of surface receptor activity in PMN resulted from a loss of receptors from the membranes or from inactivation or internalization of receptors, opsonized E were incubated in the supernatants from stressed PMN. On subsequent incubation with healthy PMN, these E made fewer rosettes than control opsonized E. The inhibitory effect of the supernatants on rosetting of IgG-sensitized E could be removed by preincubation with IgG bound to Sepharose 4B. Immunoprecipitation of C3b and C3bi receptors from surface-iodinated, osmotically stressed, and control PMN suggested that about 50% of cell surface complement receptors were lost from the cell surface during osmotic stress. These experiments suggest that receptors for IgG and C3 are extruded from PMN cell membranes as a result of hyperosmotic stress, which is associated with the freeze-thaw cycle. This may be an early event in the functional damage done to PMN during attempts at cryopreservation.