bluuebunny/crossref_metadata_2025_split huggingface dataset:
B Lymphocyte Subpopulations Separated by Velocity Sedimentation
Authors: Teale Judy M. , Howard M. C. , Falzon E. , Nossal G. J. V. 
Published: December 2022

Abstract
Spleen cells from unprimed adult, 7-day-old germ-free, and 3-day-old neonatal mice were separated by 1 × G sedimentation velocity, and the resulting fractions were tested in an in vitro splenic focus assay for NIP-specific precursor frequencies, kinetics of the response, and the class of antibody produced by the NIP-specific clones. The results of this study indicate that the splenic focus assay, contrary to other functional B cell assays, is able to detect the responses of small, medium, and large lymphocytes from both adult and neonatal B cell sources. Evidence is presented for a time-dependent appearance of hapten-specific clones in some of the B cell fractions. Most striking is the very large cell subset sedimenting at an s value &gt;5.5 in the adult and &gt;6.1 in the neonate which shows a progressive increase in the frequency of hapten-specific precursors. This would suggest the presence of a less mature B cell. An analysis of the class of antibody produced by the various sizes of B lymphocytes from both adults and neonates indicated that the majority of B cells in the smallest and largest cell fractions tested produce IgM only, whereas the majority of B cells in the medium-sized lymphocyte fraction produced IgM or IgM plus IgG classes.
In addition, the cycling status of adult and neonatal lymphocytes in the various size distributions was examined. It was found that the smallest lymphocyte fraction contained no detectable lymphocytes in rapid cell cycle. The largest lymphocyte fraction, on the other hand, was enriched for cycling cells over unfractionated controls, and in the neonatal fraction the majority of lymphocytes were in rapid cell cycle. The splenic focus assay is presumably capable of detecting a wide range of B cell subsets as defined by the criteria above including less mature B cells and is therefore a very useful cloning assay for studying B cell development.
B Lymphocyte Subpopulations Separated by Velocity Sedimentation
Authors: Teale Judy M. , Howard M. C. , Nossal G. J. V. 
Published: December 2022

Abstract
Neonatal and adult splenic B lymphocyte subpopulations, separated by velocity sedimentation, were tested in an in vitro splenic focus assay for their susceptibility to tolerance induction with hapten-protein conjugates. At least two tolerizable B cell subsets have been defined in the neonatal spleen; one comprising the slowly sedimenting, small lymphocytes and the other comprising the very rapidly sedimenting, large lymphocytes. In addition, a rapidly sedimenting large B cell subset in the adult spleen was found to be highly susceptible to tolerance induction. It was suggested that the inability to detect this susceptibility in unfractionated adult spleen was due to the low proportion of these very large lymphocytes in the total spleen cell population. The tolerizable B cell subsets presently defined probably represent the least mature B lymphocytes detectable in the splenic focus assay.
EAC Rosette-Forming Lymphocytes in Commercial Preparations of Sheep Erythrocytes
Authors: O'Neill Peggy A. , Woodson Dora L. , Mackler Bruce F. 
Published: December 2022

Abstract
In vitro enumeration of human complement (C3) receptor-bearing lymphocytes is routinely performed with sheep erythrocytes (E) sensitized with 19S anti-sheep erythrocyte antibody (A) and fresh mouse complement (C), termed the EAC reagent (1). Sheep whole blood diluted with an equal volume of Alsever's solution is washed with saline and used to prepare the EAC reagent. It is assumed that the residual sheep leukocytes in the solution are rapidly lost upon storage after the blood is collected. However, here we report finding considerable numbers of residual sheep lymphocytes in sheep blood in Alsever's solution up to 30 days after storage at 4°C. In addition, one finds that about 75% of these residual sheep lymphocytes form autorosettes with the EAC reagent.
Preparations of whole sheep blood diluted with an equal volume of Alsever's solution were obtained from a commercial source, and samples were assessed for the presence and viability of lymphocytes starting with the day the blood was drawn and continuing for 4 weeks.
Immune-Type Interferon-Induced Transfer of Viral Resistance
Authors: Blalock J. E. , Georgiades J. , Johnson H. M. 
Published: December 2022

Abstract
Mouse immune-type interferon (type II), a lymphokine, caused the transfer of viral resistance from mouse L cells to human WISH cells. The interferon was incapable of protecting WISH cells in the absence of L cells. The transfer of viral resistance occurred with interferon preparations of various specific activities, and was in proportion to the interferon concentration in te preparations. The transferred resistance had the characteristics of an interferon-induced antiviral state in that it was blocked by actinomycin D, effective against different types of viruses, and resulted from an action on the cell rather than on the virus. Mouse immune-type interferon was more efficient than virus-type (type I) at eliciting the transfer of protection. The transfer phenomenon may represent a mechanism for amplification of the interferon system as a host defense against viral infection. Further, it serves as a model for studying the mechanism of lymphokine-induced transfer of information between cells.
Physiology of Mixed Leukocyte Reaction Suppressor Factor
Authors: Belmont John W. , Rich Robert R. , Rich Susan Solliday 
Published: December 2022

Abstract
The secretory physiology of the T cell-produced lymphokine, mixed leukocyte rection suppressor factor (MLR-TsF), was characterized with respect to its kinetics of secretion and its sensitivity to a variety of metabolic blocking agents. It was found that spleen cells from alloantigen-immunized mice released active MLR-TsF after freeze-thaw lysis. Upon restimulation with the same priming alloantigen, MLR-TsF was secreted into culture supernatants, and the rate of secretion was determined to be nearly constant. Although colchicine and vinblastine, which bind to microtubules, are known inhibitors of lectin-induced proliferation, it was demonstrated that these drugs had no effect on the secretion of MLR-TsF. However, cytochalasin B, an inhibitor which also binds to some cytoskeletal and membrane-associated proteins, did inhibit the production of MLR-TsF. The above findings indicated that the activation-secretion mechanism of MLR-TsF was much like that described for lymphotoxin and macrophage migration inhibition factor. The dissociation between DNA synthesis and lymphokine secretion was also demonstrated in the MLR-TsF system. DNA synthesis plays no role in the in vitro production of suppressor factor, as determined by resistance to treatment with mitomycin C and γ-irradiation. However, new protein synthesis is required as indicated by the potent inhibitory effects of cycloheximide. Experiments utilizing timed addition and removal of cycloheximide defined a broad period of drug sensitivity, starting from the beginning of culture and lasting for 12 to 16 hr. In addition, experiments measuring the effect of cycloheximide on the MLR-TsF content of cell lysates demonstrated that the cell-associated lymphokine activity is lost when protein synthesis is interrupted. These experiments support the conclusion that MLR-TsF is synthesized de novo in culture. In addition, the secretory process itself may require protein synthesis.
Inhibition of T Cell-Mediated Cytolysis by 2-Deoxy-D-Glucose (2-DG): Differential Effect of 2-DG on Effector Cells Isolated Early or Late After Alloantigenic Stimulation in Vitro
Authors: MacDonald H. Robson , Cerottini Jean-Charles 
Published: December 2022

Abstract
The effect of the hexose analogue 2-deoxy-D-glucose (2-DG) on the functional activity of various populations of cytolytic T lymphocytes (CTL) has been compared. Under aerobic conditions, CTL harvested at the peak of the response (day 4) in primary or secondary mixed leukocyte cultures (MLC) were much more readily inhibited by 2-DG than CTL obtained from MLC at later times (day 11 to 18) or from the peritoneal cavity of alloimmune mice. Quantitatively, 0.4 mM 2-DG was sufficient to inhibit cytolysis by 50% in day 4 CTL populations, whereas 25 mM had little or no effect on day 11 to 18 CTL. Evidence was obtained that inhibition of cytolysis by 2-DG under these conditions was accompanied by a parallel inhibition of effector:target cell binding. In contradistinction to these findings, the cytolytic activity of both day 4 and day 11 MLC cells was readily inhibited by 2-DG under conditions where cell respiration was blocked by sodium azide. Furthermore, uptake of radiolabeled 2-DG was observed under aerobic conditions in both day 4 and day 11 MLC cells. These results strongly suggest that inhibition of cytolysis by 2-DG under aerobic conditions is mediated via a direct effect on CTL which is independent of the consequences of energy depletion. An indirect method by which CTL may be inhibited by 2-DG is suggested.
Release of E-Rosette Augmenting Factor (E-RAF) After Stimulation of Human Leukocytes with Mitogens or Antigens
Authors: Agbata Anthony I. , Kirkpatrick Charles H. 
Published: December 2022

Abstract
Stimulation of human peripheral blood leukocytes (HPBL) with mitogens such as phytohemagglutinin or concanavalin A increases the total number of lymphocytes that form rosettes with sheep erythrocytes. A similar effect is seen when HPBL from skin test-positive, but not skin test-negative, donors are stimulated by a specific antigen. It was also found that the culture fluids from mitogen-stimulated lymphocytes contained a substance that significantly increased the percentage of E-rosette forming cells (85 to 95%) over that of control culture fluids (40%). A similar phenomenon was also observed with supernatant fluids derived from antigenic stimulation of cells from skin test-positive donors, but not from skin test-negative subjects.
The factor that produces this effect has been designated E-rosette augmenting factor (E-RAF). It is nondialyzable; it appears in the supernatants of antigen or mitogen-stimulated cells within 12 hr; and its production is not blocked by mitomycin C. It is produced by cells that do not adhere to glass wool columns and by mitogen-stimulated thymocytes. Sephadex G-100 chromatography showed that mitogen-induced E-RAF eluted from the column in advance of antigen-induced E-RAF. E-RAF has many properties that are characteristic of lymphokines.
Human Transfer Factor: Structural Properties Suggested by HPRP Chromatography and Enzymatic Sensitivities
Authors: Burger Denis R. , Vandenbark Arthur A. , Dunnick Wesley , Kraybill William , Daves G. Doyle , Vetto R. Mark 
Published: December 2022

Abstract
Leukocyte extracts containing human transfer factor (TF) were fractionated by exclusion chromatography, and the active fraction (Sephadex G25, Fraction IIIa) was subjected to high pressure, reverse phase (HPRP) chromatography and enzymatic degradation. TF activity was assessed by the systemic transfer of dermal skin test reactivity from KLH-immunized donors to naive recipients. Preparative HPRP chromatography resolved Fraction IIIa into multiple chromophoric regions, two of which demonstrated transfer of KLH reactivity. Alkaline phosphatase treatment of Fraction IIIa converted the major ultraviolet-absorbing component, 5′-inosine monophosphate, to inosine and resulted in TF activity being restricted to one region. This HPRP region (R1A) contained less than 1% of the UV254 active material in Fraction IIIa but greater than 90% of the reactivity.
The sensitivity of TF to pronase, proteinase K, phosphodiesterase I, and phosphodiesterase II was evaluated by inhibition of systemic transfer of KLH reactivity. Pronase and proteinase K destroyed systemic transfer activity and the pronase destruction could be inhibited with traysylol. Phosphodiesterase I, a 3′ exonuclease, destroyed activity, whereas phosphodiesterase II, a 5′ exonuclease, did not. The data are consistent with a phosphodiester-containing polypeptide in the structure of human TF for KLH reactivity.
The Immunochemistry of Antibodies Sharing Concanavalin A's Anti-Mannosyl Binding Specificity
Authors: Reichert Cheryl M. , Goldstein Irwin J. 
Published: December 2022

Abstract
Procedures were developed for the synthesis of the disaccharide hapten, p-isothiocyanatophenyl 2-O-α-D-mannopyranosyl-α-D-mannopyranoside, and for its conjugation to hemocyanin. The synthetic carbohydrate: protein antigen was then emulsified in complete Freund's adjuvant and injected into the footpads of New Zealand White rabbits. A population of the resulting anti-conjugate antibodies displayed some binding properties analogous to concanavalin A, the carbohydrate-binding protein of the jack bean. The antisera weakly precipitated mannans from Saccharomyces rouxii, S. cerevisiae, and an α-(1 → 3)-mannopyranosyl transferase-deficient mutant from Kluyveromyces lactis Y58a. These polysaccharides, possessing side chains containing terminal α-(1 → 2)-mannobiosyl residues, produce strong precipitation reactions with concanavalin A. In addition, various saccharides were tested for their ability to inhibit the interaction of anti-conjugate antisera with α-(1 → 2)-mannobiosyl-containing polymers. p-Nitrophenyl 2-O-α-D-mannopyranosyl-α-D-mannopyranoside showed a strong complementarity for the binding sites of both the anti-conjugate antisera and concanavalin A. However, the antibody failed to bind a concanavalin A-reactive mouse fibrosarcoma or to stimulate mitogenesis of human peripheral lymphocytes.
Further Characterization of Thymic Suppressor Cells and a Factor That Suppress the Generation of Cells Cytotoxic for a Syngeneic Tumor in DBA/2 Mice
Authors: Levy Julia G. , Maier Thomas , Kilburn Douglas G. 
Published: December 2022

Abstract
Antigen-specific suppressor cells and suppressive extracts obtained from the thymuses of DBA/2 mice bearing small syngeneic P815 mastocytomas were compared for their immunogenetic properties and requirements. The assay for specific suppression involved the ability of either cells or extracts to inhibit the primary in vitro cytotoxic response of normal DBA/2 splenocytes to mitomycin-treated P815 cells. It was shown that pretreatment of suppressor cell populations with anti-Iad antiserum plus rabbit complement removed the suppressive activity. Similarly, absorption of the suppressive factor with anti-Iad antiserum removed the suppressive properties of the material. It was found that the suppressor cells, generated in DBA/2 tumor bearers, were capable of specifically suppressing the anti-P815 response of B6D2 F1 radiation chimeras possessing lymphoid cells of the H-2b or H-2t2 haplotype equally as well as they could suppress the response of H-2d-bearing effector cells. This indicates that the suppressor cells are not H-2 restricted with respect to K or D markers on the responder cells in this system.
Influence of Different Routes of Anti-Tumor Immunization: Alternative Induction of Tumor Immunity and Tumor Enhancement
Authors: Bauer Heinz , Hayami Masanori , Stehfen-Gervinus Johannes C. 
Published: December 2022

Abstract
Chickens and quails were immunized in parallel either i.v. or intramuscularly (i.m.) with lectin column-purified antigens from chick embryo cells that were transformed in vitro by avian sarcoma virus (ASV). After five to six injections, immunity of the animals was tested by challenge with ASV into the wing webs. Whereas tumor growth was inhibited after i.v. immunization with respect to incidence rate and time of tumor appearance, tumor growth was enhanced after i.m. injection. Animals that were injected with normal cell antigens served as controls. Spleen cells from only those animals that were immunized i.v. exerted a cytotoxic effect in vitro against ASV-transformed cells, whereas spleen cells from i.m. injected animals, in contrast, suppressed such cytotoxicity. The search for serum blocking or arming factors suggested that sera from i.m. injected animals block cellular cytotoxicity whereas sera from i.v. immunized animals render normal spleen cells cytotoxic (arming effect). The use of viruses from different subgroups and of antigens from gp85-lacking ASV-transformed cells indicates that immune effects were obtained against tumor cell surface antigens that differ from the antigen that is involved in virus neutralization (s-gp85).
Structural Comparison of Murine Ia Antigens Determined by the I-A and I-E Subregions
Authors: Cullen Susan E. , Kindle Cathy S. , Littman Dan R. 
Published: December 2022

Abstract
After nonionic detergent solubilization, the Ia molecules determined by the I-A subregion are distributed between a covalently linked “58K” structure composed of one α chain (35,000 daltons) and one β chain (25,000 daltons) separable by treatment with SDS and mercaptoethanol, and a form in which α and β chains are separable by treatment with SDS alone (α, β form). In contrast, the Ia molecules determined by the I-E subregion have α and β chains that are not covalently linked, and can be entirely separated by SDS-PAGE under rigorous (100°C) dissociating conditions without reducing agent. Milder dissociating conditions (37°C) permitted observation of a noncovalently linked 58K form for I-E molecules. Therefore, in their native state, both I-A and I-E molecules probably are composed of associated α and β chains.
Iodoacetamide treatment of intact cells before detergent solubilization decreased the fraction of I-A molecules in the covalently linked 58K form. This finding probably means that the covalent linkage is an artifact of solubilization, but because it is restricted to I-A molecules, there still must be an underlying structural difference between I-A and I-E molecules. Selective destruction by iodoacetamide of the antigenic activity of the 58K form of I-A molecules could also account for the loss in 58K form, but only if there is an iodoacetamidesensitive antigenic and/or structural difference between I-A molecules in the 58K and α, β form. We compared these two forms by isoelectric focusing, but found no clear differences between them.
The Fine Specificity of Regulatory T Cells
Authors: Adorini Luciano , Miller Alexander , Sercarz Eli E. 
Published: December 2022

Abstract
We have demonstrated the induction of suppressor T cells of highly restricted specificity in a nonresponder strain. HEL (hen egg-white lysozyme) fails to elicit an antibody response in C57BL/10 (B10) mice whereas the closely related REL (ring-necked pheasant egg-white lysozyme) is strongly immunogenic. However, an anti-HEL primary antibody response can be obtained in B10 mice in vivo or in vitro by coupling HEL to red blood cells (RBC). Preimmunization with HEL-CFA induced reduction of the anti-HEL PFC response to a subsequent challenge with HEL-RBC. Suppression was demonstrated by in vitro mixing experiments and was mediated with remarkable efficiency by I-J positive suppressor T cells. Suppression was specific for the anti-HEL response and did not affect the anti-RBC response. Both IgM and IgG anti-HEL in vivo antibody responses showed 70 to 80% suppression. Relatively high doses of antigen were required to generate efficient suppression. Optimal suppression was reached within 4 weeks after HEL priming and remained maximal at least 9 weeks after priming. Fine specificity in the expression of suppressive activity was displayed by HEL-specific suppressor cells that were not able to suppress an anti-REL response. Furthermore, REL priming did not suppress an in vitro anti-HEL response to HEL-RBC. The close similarity in amino acid sequence and in B cell cross-reactivity between HEL and REL, contrasted with the lack of REL recognition by HEL-specific suppressor T cells, indicates that a limited region on the nonimmunogenic HEL, absent on REL, can account for the induction of suppression.
Secretory Component: Interactions with Intracellular and Surface Immunoglobulins of Human Lymphoid Cells
Authors: Crago Sylvia S. , Mestecky Jiri 
Published: December 2022

Abstract
Unstimulated and PWM-stimulated lymphocytes from normal human peripheral blood, cord blood, peripheral blood of patients with panhypogammaglobulinemia and selective IgA deficiency, as well as human lymphoblastoid cell lines were examined for their ability to bind secretory component (SC) on the surface and in the cytoplasm. SC binding was not detected on the cell surface at any stage of differentiation in these cells. However, binding of SC was detected in the cytoplasm of 2.3% of normal peripheral blood lymphocytes cultured in the presence of PWM for 6 to 7 days, and in two IgA-producing lymphoblastoid cell lines. The capability of lymphoid cells to bind SC was not concurrent with J chain production. Although IgA was detected in the cytoplasm of PWM-stimulated lymphocytes from IgA-deficient patients, these cells did not bind SC. The failure to detect surface receptors indicates that SC is not a probable factor determining the homing of IgA precursor cells into exocrine tissues.
Cyclical Changes in Susceptibility of A Myeloma Tumor (LPC-1) to Immune Destruction
Authors: Hale Arthur H. , Celis Esteban , Rusell John H. , Eisen Herman N. 
Published: December 2022

Abstract
Cells of the LPC-1 myeloma tumor (of BALB/c origin) were tested periodically for susceptibility to lysis by anti-H-2 cytotoxic T lymphocytes (CTL) and by complement-dependent anti-H-2 antibodies (Ab), and for ability to adsorb these Ab, as the cells grew in culture and in ascites form in nude (BALB/c·nu) and in normal BALB/c mice. Cells harvested from 2 to 8 days after inoculation into the peritoneal cavity had the “early” phenotype: they were extensively lysed by the CTL and Ab and effectively adsorbed the Ab. Cells harvested on day 8 and afterward had the “late” phenotype: they were not lysed by CTL, required more Ab for lysis, and had about 8-fold less ability (per cell) to adsorb the Ab. All of these activities were completely reversed 2 to 4 days after transferring late cells into fresh BALB/c hosts. LPC-1 cells growing in nude BALB/c mice also changed from the early, CTL-susceptible to the late CTL-resistant phenotype. With repeated cell counts and measurements of 125I-iododeoxiuridine incorporation to estimate growth, it was found that exponentially growing cells had the early phenotype and that cells in stationary phase had the late phenotype. When placed in culture, the early cells retained their phenotype indefinitely (up to 40 days). However, the late cells switched phenotype: initially resistant to CTL and Ab, after 1 to 4 days in culture they became fully susceptible to CTL and highly reactive with the Ab, and these features persisted in culture thereafter. This transition occurred even when the late, resistant cells were prevented from dividing in culture by prior irradiation (10,000 R) or by trinitrophenylation with 2,4,6-trinitrobenzenesulfonic acid. The findings in both nude mice and in culture indicate that the reversible, early-late phenotypic changes are due to changes in individual cells, rather than to immunoselection of preexisting variant cells.
Three Suppressor Systems in Human Blood That Modulate Lymphoproliferation
Authors: Rice Lawrence , Laughter Arline H. , Twomey Jeremiah J. 
Published: December 2022

Abstract
Three suppressor systems of T lymphocyte proliferation found in normal blood were characterized. The adherent cell suppressor system (ACSS) is effected by a steroid and radioresistant monocyte that survives well in culture. The prostaglandin-related suppressor system (PgSS) is effected by a similar cell but is distinct from the ACSS in terms of magnitude of suppression, effective monocyte concentration, and carrageenan or indomethacin sensitivity. The induced suppressor system (ISS) is effected by a T lymphocyte that is partially radiosensitive and loses activity after 24 hr in culture. Although the ISS is unaffected by age, ACSS and PgSS activity is, overall, higher among elderly than among young adult subjects. Activation of these three suppressor systems does not require cell replication. They are not restricted by histocompatibility barriers.