bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Quantitative Study at the Single Cell Level of Immunoglobulin Antigenic Determinants Present on the Surface of Murine B and T Lymphocytes
Authors: Avrameas Stratis , Hösli Peter , Stanislawski Marc , Rodrigot Maryvonne , Vogt Esther 
Published: January 2023

Abstract
An enzyme-immunoassay for the quantitation at the single cell level of immunoglobulin antigenic determinants present on the membrane of murine lymphocytes (MIg) has been developed. This immunoassay makes use of specific Fab:anti-Ig, anti-κ, anti-µ, and anti-γ conjugated to Escherichia coli β-galactosidase of high specific activity in conjunction with the micromanipulation of lymphocytes and the measurement of enzyme activity with the fluorogenic substrate 4-methylumbelliferyl-β-D-galactopyranoside with a microassay system. With this technique MIg was detected and could be measured in substantial amounts on the surface of almost all splenic and lymph node lymphocytes examined. Depending on the specific Fab employed, 0 to more than 79,000 MIg per lymphocyte were measured, but a larger proportion of cells with higher amounts of MIg were found in spleen than in lymph nodes. However, when the same Fab′s were used to localize MIg by a conventional immunohistochemical staining, only a fraction of cells, corresponding to published values, could be scored as positive.
The fact that MIg was associated with the vast majority of lymphoid cells implied that T cells carried such antigens. In order to investigate this further, experiments were performed on splenic B and T cell fractions obtained either with an anti-Ig immunoadsorbent or after treatment with anti-θ serum plus complement. The B cell fraction possessed greater amounts of MIg (1500 to 79,000) than the T cell fraction (0 to 39,000). However, on the average, B cells carried only 2 to 2.5 times more µ, κ, and γ antigenic determinants than T cells. Thus, B cells carried a mean of 27,300 to 47,800 Ig, 17,400 to 30,400 κ, 13,000 to 23,000 µ, and 4200 to 7300 γ antigenic determinants on their surface. T cells carried 4600 to 8000 Ig, 7200 to 12,600 κ, 5600 to 9800 µ, and 2400 to 4200 γ determinants. Immunoabsorbent column-fractionated T cells from which MIg was removed by anti-mouse Ig stripping were able to regenerate MIg after 24 hr of culture. The quantities reexpressed were equal to those found on T cells before anti-Ig treatment. These results strongly suggest that T cells synthesize and express MIg.
Two nonmutually exclusive hypotheses are advanced that may account for the observations made: 1) Irrespective of the molecular nature of the T cell structure detected in this study, it is proposed that the difficulty in detecting MIg by standard immunohistochemical staining methods may reflect differences in the membrane composition of B and T cells. Local concentrations of MIg on B cells could be higher than on T cells, or a microredistribution of MIg may be achieved more easily on B than on T cells. 2) The T cell MIg may be conceived of as a molecule structurally different from the MIg on B cells.
Identification of the Platelet Activating Activity in Rheumatoid Synovial Fluid as an Intermediate Molecular Weight Complex of IgG
Authors: Valone Frank H. , Austen K. Frank , Goetzl Edward J. 
Published: January 2023

Abstract
The predominant platelet-activating activity assessed by the release of 14C-serotonin from washed human platelets was purified from the synovial fluid of patients with rheumatoid arthritis. Cation exchange chromatography on carboxymethyl cellulose, gel filtration on Sepharose 6B and preparative isoelectric focusing yielded a single factor with an apparent m.w. of 450,000 and an isoelectric point of 8.36 ± 0.25 (mean ± S.D.). Homogeneity of the purified synovial fluid platelet-activating activity, termed SF-PAA, was confirmed by the complete correspondence between platelet-activating activity and protein during gel filtration and electrophoresis in a glycerol gradient and by the elicitation of a monospecific antiserum. Platelet activation by SF-PAA, although coupled to serotonin secretion, was not associated with the release of the cytoplasmic marker lactic acid dehydrogenase or with platelet aggregation. Ouchterlony analysis of SF-PAA revealed a line of complete identity with human IgG with antiserum to either SF-PAA or γ heavy chains. Kappa and λ light chains were also identified in SF-PAA, whereas µ and α heavy chains, fibrinogen, and the complement components, Clq, C3, properdin, and B, were not present. Thus, SF-PAA appeared to be a complex of IgG of average m.w. 450,000. The inhibition of its action by monomeric IgG confirmed that the complex activated platelets through an IgG receptor.
Immunodeficiency with Thymoma: Failure to Induce Ig Production in Immunodeficient Lymphocytes Cocultured with Normal T cells
Authors: Litwin Stephen D. 
Published: January 2023

Abstract
Blood mononuclear cells of two individuals having immunodeficiency with thymoma (ID-THY) were cocultured with normal mononuclear cells or treated mononuclear cell fractions in an attempt to correct an imbalance of regulatory cells postulated to be responsible for the failure of pokeweed mitogen-induced Ig synthesis in vitro. Treatment included abrogation of suppressor cell activity by irradiation or incubation with prednisilone in vitro. T cell help was provided by cocultivating lymphocytes of related and unrelated persons, and in some cases autologous treated cells. Ig secretion failed to be induced by any experimental maneuver suggesting that the primary problem in the above ID-THY cells was related to defective or deficient B cells rather than an imbalance of T regulatory cells.
Prednisilone treatment in vitro decreased suppressor cell activity in allogeneic cocultures of two ID-THY persons (S1 and S2) but not of an individual (S3) with variable immunodeficiency suggesting heterogeneity of suppressor cells.
Effects of marrow donor and recipient age on immune responses.
Authors: Astle C M , Harrison D E 
Published: January 2023

Abstract
This report describes treatments to restore diminished splenic immune responses of old mice. Lethal irradiation, followed by young bone marrow and infant thymus transplants, restored the T cell mitogen response and the antibody-forming cell response against sheep red blood cells in the old mice. Although old bone marrow cells restore these immune responses in young recipients, as well as do young bone marrow cells, old bone marrow in old recipients did not improve their levels of response. Longevities of old recipients with rejuvenated responses were not increased, and aging of tail tendon collagen was not affected. The effect of lethal irradiation before the marrow transplant was shown to be minimal, by the use of unirradiated old W-anemic recipients. Parabiosing young mice with old partners caused impairment of these two immune responses in the young partners without enhancing them in the old partners. The old partners did not have increased longevities. To explain these results, we suggest the following hypothesis: old bone marrow contains precursors that produce suppressive factors or cells when in an old environment but not when in a young environment. However, these factors, if allowed to develop in an old environment, can function in a young parabiosed partner.
Antigenic modulation of junctional acetylcholine receptor is not sufficient to account for the development of myasthenia gravis in receptor immunized mice.
Authors: Berman P W , Heinemann S F 
Published: January 2023

Abstract
Myasthenia gravis (MG) is a disease thought to result from an autoimmune response against the nicotinic acetylcholine receptor of the neuromuscular junction. Although there is little doubt that the muscular weakness characteristic of MG can be attributed to an antibody-mediated reduction in the density of AChR, the mechanism responsible for this reduction remains uncertain. In the present studies we have used a mouse model of MG, termed experimental myasthenia gravis (EMG), to test the possibility that antigenic modulation of AChR may be the principle mechanism whereby this reduction in AChR density is achieved. We found that immunization of mice with AChR, on average, leads to a twofold increase in the rate of junctional AChR degradation. Because this effect occurred to the same extent in mice that developed severe paralysis and in those that gave no indication of muscular weakness, the role of antigenic modulation as a major pathologic mechanism in MG is questioned.
FcR epsilon+ lymphocytes and regulation of the IgE antibody system. III. Suppressive factor of allergy (SFA) is produced during the in vitro FcR epsilon expression cascade and displays corollary physiologic activity in vivo.
Authors: Marcelletti J F , Katz D H 
Published: January 2023

Abstract
Exposure of lymphoid cells to IgE induces the expression of Fc receptors for IgE (FcR epsilon) and the production of soluble mediators, termed IgE-induced regulants (EIR). Conventional suppressive factor of allergy (SFA) and enhancing factor of allergy (EFA), derived from mouse ascites fluids, both inhibit IgE-induced FcR epsilon expression in vitro in cultures of unfractionated and T cell-enriched, but not B cell-enriched, lymphoid cells. This indicates that the inhibitory activities of both entities are T cell dependent, and distinguishes them from the inhibitory EIRI, which inhibits FcR epsilon induction in the absence of T cells. Moreover, SFA and EFA can be distinguished from one another by differences in the T cell subsets required for the inhibitory activity of each respective mediator on in vitro IgE-induced FcR epsilon expression. Thus, SFA requires the presence of Lyt-1+ T cells, whereas EFA requires the presence of Lyt-2+ T cells. Supernatant fluids from IgE-stimulated unfractionated lymphoid cell cultures suppress in vivo IgE synthesis in mice, indicating that SFA is produced along with the other species of EIR. To define conditions required for SFA production in vitro, EIR-rich supernatant fluids were tested for the presence of SFA by using Lyt-2+ cell-blocked indicator cells in the in vitro FcR epsilon induction assay system (this eliminates the inhibitory activity of EFA). SFA production in vitro by IgE-stimulated lymphoid cells was shown to result from cooperative interactions between B cells and Lyt-1+ T cells. In addition, as observed with the induction of FcR epsilon in general, induction of SFA requires the initial interaction of B cells with IgE, and the release of the B cell-selective EIRB. Once produced, EIRB can directly stimulate Lyt-1+ cells, but not Lyt-2+ cells, to produce SFA. The physiologic significance of the in vitro induction of SFA by the action of EIRB on Lyt-1+ cells was confirmed by the demonstration that EIRB, devoid of detectable SFA, selectively suppressed in vivo IgE synthesis after administration to intact mice. This indicates that EIRB can stimulate resident T cells of irradiated SJL mice to produce SFA. Finally, as shown previously with conventional ascites-derived SFA, the SFA produced in vitro after stimulation of lymphoid cells with IgE is devoid of IgE-binding properties, because its inhibitory effects on in vivo IgE antibody synthesis are not removed by passage over IgE affinity columns.
Helper T lymphocytes from xid and normal mice support anti-phosphocholine antibody responses with equivalent T15, 511, and 603 idiotypic composition.
Authors: Feeney A J , Mosier D E 
Published: January 2023

Abstract
We have examined the idiotypic composition of secondary adoptive transfer antibody responses to phosphocholine (PC) supported by KLH-primed helper T cells derived from normal mice or xid mice. CBA/N x BALB/c F1 male xid mice have diminished anti-PC responses and virtually undetectable levels of the T15 idiotype; xid mice do express the 511 and 603 idiotypes. Nonetheless, we find helper T cells derived from such mice are indistinguishable from T cells primed in a normal environment in their ability to cooperate with B cells producing anti-PC antibody bearing the T15, 511, or 603 idiotype markers. This result is in contrast to a previously published report from this laboratory. T cells from xid mice did support more IgG PFC than normal T cells, but serum IgG anti-PC antibody levels were similar in both groups. The IgM anti-PC response was predominantly of the T15 idiotype, whereas the 511 idiotype was associated with a minor fraction of IgG1 antibodies. The majority of the secondary IgG "anti-PC" antibody response bore none of the idiotypic markers associated with PC-binding myeloma or hybridoma antibodies, and was directed against phenyl-PC rather than PC. The phenomenon of T15 clonal dominance in the anti-PC response therefore is largely confined to the IgM response. We would conclude that the idiotype levels in the T cell priming environment do not influence the subsequent ability of such primed T cells to support anti-PC antibody responses.
Cholera toxin feeding did not induce oral tolerance in mice and abrogated oral tolerance to an unrelated protein antigen.
Authors: Elson C O , Ealding W 
Published: January 2023

Abstract
The feeding of protein antigens to mice results in a state of tolerance when feeding is followed by parenteral immunization. Cholera toxin (CT) is a protein that has been used extensively as a potent oral immunogen for mucosal IgA responses, but CT feeding also stimulates a substantial plasma IgG antibody response. This latter finding prompted us to study whether or not CT induces oral tolerance. Mice were fed 5 mg keyhole limpet hemocyanin (KLH) or 10 micrograms CT at least twice before parenteral immunization with 1 microgram KLH or CT in alum i.p. Plasma and intestinal secretions were collected at intervals. The specific IgG or IgA antibody in the samples was measured by ELISA. Although KLH feeding did induce oral tolerance, CT feeding did not induce oral tolerance in any of three mouse strains tested or at any dose of CT given orally. The feeding of the B subunit of CT did not result in oral tolerance either. When both CT and KLH were fed together, CT was able to abrogate oral tolerance to KLH, an antigenically unrelated protein. Moreover, feeding CT along with KLH stimulated secretory IgA anti-KLH responses, whereas no such IgA responses were found when KLH was given alone. Thus, in these experiments with protein antigens, IgA immunization and oral tolerance were reciprocally linked and did not occur simultaneously. CT appears to abrogate oral tolerance and to stimulate secretory IgA responses by altering the regulatory environment in gut-associated lymphoid tissue, shifting it toward responsiveness.
Newborn and Wiskott-Aldrich patient B cells can be activated by TNP-Brucella abortus: evidence that TNP-Brucella abortus behaves as a T-independent type 1 antigen in humans.
Authors: Golding B , Muchmore A V , Blaese R M 
Published: January 2023

Abstract
TNP-Brucella abortus (TNP-Ba) has been classified as a T-independent type 1 (TI-1) antigen in the mouse on the basis that it activates neonatal and CBA/N (X-linked immunodeficient) murine B cells in contrast to T-independent type 2 (TI-2) antigens. Therefore, it was of interest to determine whether human newborn and X-linked Wiskott-Aldrich syndrome B cells could be triggered by TNP-Ba. Previous studies had shown that human B cells from both these latter sources were relatively insensitive to stimulation with T-dependent and polysaccharide antigens (TI-2 in mouse). In this study, we show that TNP-Ba can trigger human cord blood B cells to differentiate into anti-TNP plaque-forming cells (PFC) in a hapten-specific and T-independent manner. The dose response and kinetics were similar to those previously seen with adult cells. The newborn responses, however, were lower than adult PFC responses. Precursor frequency and clone size analyses revealed that this lower response was not due to newborn cells containing fewer precursors but was the result of a reduced ability of these anti-TNP clones to expand. The ability of TNP-Ba to activate immature newborn B cells implies that this antigen can be used to assess B cell function in very young children. It also implies that TNP-Ba behaves as a TI-1 antigen in humans as well as in mice. This was supported by the finding that B cells from Wiskott-Aldrich patients, which were unreactive to polysaccharide antigens, were generally responsive to TNP-Ba. Therefore, it would appear that human newborn and Wiskott-Aldrich patients do possess a functionally competent B cell subset possibly equivalent to Lyb-5- immature murine B cells.
Regulation of interleukin 2 receptor expression: effects of phorbol diester, phospholipase C, and reexposure to lectin or antigen.
Authors: Depper J M , Leonard W J , Krönke M , Noguchi P D , Cunningham R E , Waldmann T A , Greene W C 
Published: January 2023

Abstract
Anti-Tac monoclonal antibody identifies the receptor for interleukin 2 (IL 2, or T cell growth factor) present on activated human T lymphocytes. By using tritiated anti-Tac, we now report a sensitive and specific binding assay to evaluate cell surface IL 2 receptor expression. IL 2 receptors on human peripheral blood lymphocytes can be detected within 6 hr after PHA stimulation. PHA-induced receptor expression is inhibited by actinomycin D and cycloheximide, but not by mitomycin C, suggesting a requirement for de novo RNA and protein synthesis, but not DNA synthesis. Scatchard analysis of [3H]-anti-Tac binding to lymphocytes stimulated with PHA for 3 days revealed from 20,000 to 60,000 molecules of antibody bound per cell, and a Kd of 1 to 3 x 10(-10) mol/l. Sequential binding studies of activated human lymphocytes maintained in long-term culture with IL 2 demonstrated a progressive decline in receptor number correlating with diminished growth rate. Restimulation with lectin or antigen increased the number of IL 2 receptors, suggesting that IL 2 dependent immune responses may be regulated, at least in part, by IL 2 receptor expression. Receptor number was also increased by PMA. Moreover, similar effects were produced by incubation with phospholipase C but not interleukin 1. Because both PMA and phospholipase C result in activation of protein kinase C, these data suggest the possibility that activation of protein kinase C may induce IL 2 receptor expression.
Demonstration of the involvement of interleukin 2 in the differentiation of Staphylococcus aureus Cowan I-stimulated B cells.
Authors: Teranishi T , Hirano T , Lin B H , Onoue K 
Published: January 2023

Abstract
The effect of IL 2 on Staphylococcus aureus Cowan I (SAC)-driven IgG production of human B cells was examined by utilizing chromatographically purified IL 2 (R-IL 2) and the transcription product of the cloned cDNA for human IL 2 purified from recombinant E. coli (G-IL 2). Both preparations of IL 2 by themselves were not enough to induce optimal IgG-production in the SAC-stimulated tonsillar B cell fraction, which was highly enriched for B cells, but effectively induced IgG production in the presence of a subeffective number of T cells or a late-acting B cell differentiation factor (BCDF). In addition, the activity that induced IgG production in the presence of a subeffective number of T cells was absorbed with an IL 2-dependent mouse T cell line. These results clearly indicate that IL 2 has a definite effect on B cell differentiation in this system. Although the mechanisms of this effect remain to be elucidated, a direct effect of IL 2 on B cells may be involved, because the addition of IL 2 along with SAC induced a limited but significant increase of 3H-TdR incorporation in the highly enriched B cell population, which showed very little response to PHA and Con A even in the presence of IL 2, and, as mentioned above, IL 2 induced IgG production in the B cell preparation without any supplement of T cells provided the late-acting BCDF fraction was present in the culture.
Chemical and serologic definition of two unique D region-encoded molecules in the wild-derived mouse strain B10.GAA37.
Authors: Lillehoj E P , Walsh W D , Potter T , Lee D R , Coligan J E , Hansen T H 
Published: January 2023

Abstract
Detailed serologic and biochemical characterization of D region products of the wild-derived mouse strain B10.GAA37 (Dw16) were performed and compared with previous studies of the D region products of the H-2d,b, and q haplotypes. Serologic analysis revealed that the antigens encoded by the Dw16 region express a unique combination of specificities defined by monoclonal antibodies (mAb) with established activity for the Ld and Dd molecules. Two out of five anti-Ld-reactive mAb reacted with B10.GAA37 cells, whereas one of three anti-Dd mAb showed B10.GAA37 reactivity. Sequential immunoprecipitation of B10.GAA37 antigens demonstrated the existence of at least two antigenically distinct molecules (designated Dw16 and Lw16) encoded by genes associated with the Dw16 region. Peptide map comparisons of the Dw16 and Lw16 molecules defined multiple differences in their primary protein structure, suggesting they are products of separate genes. Structural comparisons of the Lw16 and Dw16 molecules with the Ld and Dd molecules implied a) that the Dw16 and Dd regions did not result from a recent evolutionary divergence of a common primordial haplotype, and b) that the Lw16 and Dw16 molecules are more structurally homologous to each other than the Ld and Dd molecules are. Comparison of these findings with our previous studies of antigens encoded by the D regions suggest that each of these haplotypes has unique properties in terms of the number of gene products expressed and/or the structural relatedness of products of the same region.
Binding specificities of eight monoclonal antibodies to human glycophorin A--studies with McM, and MkEn(UK) variant human erythrocytes and M- and MNV-type chimpanzee erythrocytes.
Authors: Bigbee W L , Langlois R G , Vanderlaan M , Jensen R H 
Published: January 2023

Abstract
Four newly derived mouse monoclonal antibodies to human glycophorin A are described. Three of these antibodies bind preferentially to the N form of glycophorin A; the fourth recognizes a shared determinant of the M and N forms. All four antibodies are directed toward the 39 amino acid, amino-terminal portion of the protein, and the N-specific antibodies require for binding the presence of N-acetyl-neuraminic acid on the glycosidically linked oligosaccharides. Cross-reaction of the N-specific antibodies to homozygous MM erythrocytes appears to result from binding to glycophorin B. In addition, these antibodies together with four previously reported glycophorin monoclonal antibodies, including two that specifically recognize the M form of glycophorin A, were tested for binding to McM and MkEn(UK) variant human erythrocytes and M- and MNV-type chimpanzee erythrocytes. Results obtained for five of the six M- or N-specific monoclonal antibodies point to the general immunodominance of the amino-terminal serine-leucine polymorphism and the requirement for sialic acid. One of the two M-specific monoclonal antibodies, 9A3, discriminates between the M, N, and Mc forms of glycophorin A solely on the basis of the amino-terminal serine-leucine polymorphism. The other M-specific antibody, 6A7, requires a more complex determinant involving the glycine-glutamic acid polymorphism at the fifth position in the sequence as well. The epitopes for all three N-specific monoclonal antibodies include the amino terminal leucine that occurs in the N form of glycophorin A and may also include the glutamic acid that occurs at position five. Our studies support the proposed Lepore-type glycophorin A-B hybrid gene rearrangement for the En(UK) allele found in the English En(a-) family. The data also confirm the expression of the M-like glycoprotein on chimpanzee erythrocytes and the presence of a human glycophorin B-like antigen on the MNV-type cells.