bluuebunny/crossref_metadata_2025 huggingface dataset:
Basophil-Sensitizing Antibody Response to Herpes Simplex Viruses in Rabbits
Authors: Day Richard P. , Bienenstock John , Rawls William E.
Published: December 2022

Antibodies to herpes simplex virus type 1 and type 2 were detected in the sera of rabbits by release of histamine from basophils sensitized in vitro with the sera. The time course of the appearance of the antibodies, the dose-response curve of the release of histamine in relation to antigen concentration, the sedimentation characteristics of the antibodies in sucrose gradients, and the ability to destroy the sensitizing capacity of the sera with heat suggest that the antibodies being assessed were of the IgE class. These antibodies were induced in animals injected intradermally, intramuscularly, and i.p. with live virus. The antibodies were detected 1 week after primary injection and a similar time course of antibody appearance was observed after a second or third injection. The same cross-reactivity between type 1 and type 2 virus observed with IgG antibody was also observed with IgE antibody.
In Vitro Production of IgE by Human Peripheral Blood Lymphocytes: Effect of Cholera Toxin and β Adrenergic Stimulation
Authors: Patterson Roy , Suszko Irena M. , Metzger W. James , Roberts Mary
Published: December 2022

Peripheral blood lymphocytes from two human donors with elevated serum IgE concentrations were maintained in short term tissue culture preparations. Repeated culture preparations demonstrated that IgE was produced in vitro in amounts that could be measured by the double antibody radioimmunoassay technique. The amount of IgE produced by replicate cultures of cells from a single bleeding of the donor was similar when the cultures were simultaneously prepared. In contrast, IgE production by the same donor's lymphocytes varied when the culture preparations were initiated from separate bleedings. The results of simultaneous cultures of a single bleeding were sufficiently consistent to provide a means of testing the effect of pharmacologic agents on the in vitro production of IgE. Cholera toxin effected a marked reduction in production of IgE by lymphocytes of both cell donors. Isoproterenol showed marked inhibition of IgE production at 10-3 M but cell viability studies suggested that this may have been due to decreased cell viability. At lower, nontoxic concentrations of isoproterenol (10-4 M-10-6 M) slight but definite inhibition of in vitro IgE production was evident. This inhibition was more pronounced subsequent to the first 24 hr of exposure of the cells to isoproterenol.
Induction of Resistance to Toxoplasma Gondii in Human Macrophages by Soluble Lymphocyte Products
Authors: Anderson Seth E. , Bautista Simeon , Remington Jack S.
Published: December 2022

Autoradiography and light microscopy were used to study the effects of lymphocyte culture supernatants, prepared under a variety of conditions, on the course of intracellular Toxoplasma gondii infection in human monocyte-derived macrophages in vitro. Supernatants prepared by incubating lymphocytes of dye test- (DT) positive subjects with T. gondii lysate antigen (TLA), lymphocytes of DT/negative subjects with streptokinase-streptodornase (SK-SD), or both populations of lymphocytes with concanavalin A (Con A) were capable of activating macrophages to inhibit or kill intracellular T. gondii. Supernatants prepared with the homologous antigen (TLA) to the target organism appeared more active in conferring resistance to infection with T. gondii on macrophages than those prepared with a heterologous antigen (SK-SD) or mitogen (Con A). The number of lymphocytes was critical in preparing active supernatants. These results suggest that soluble lymphocyte mediators can activate human macrophages in vitro to inhibit or kill T. gondii.
Regulation of Antibody Response in Different Immunoglobulin Classes
Authors: Kishimoto Tadamitsu , Hirai Yoshikatsu , Suemura Masaki , Yamamura Yuichi
Published: December 2022

Selective suppression of IgE antibody response was demonstrated. Preadministration of DNP-coupled mycobacterium (DNP-Tbc) inhibited the formation of anti-DNP IgE antibody induced by DNP-OA without any suppressive effect on anti-DNP IgG antibody response. Secondary anti-DNP IgE antibody response by DNP-OA was also significantly depressed by the preadministration of DNP-Tbc. Anti-OA IgE antibody response induced by DNP-OA was also depressed by DNP-Tbc, whereas anti-OA IgE antibody response induced by PAB-OA was not affected by the preadministration of DNP-Tbc. Preimmunization with DNP-MGG induced much higher anti-DNP IgG antibody response than DNP-Tbc, but DNP-MGG did not suppress the induction of anti-DNP IgE antibody. The transfer of DNP-Tbc-primed spleen cells into normal mice depressed anti-DNP IgE antibody response. B cell-depleted cell populations also showed a comparable inhibitory effect to that of unfractionated DNP-Tbc primed cells. In the adoptive cell transfer experiment, DNP-Tbc-primed cells depressed anti-DNP IgE antibody response of DNP-OA-primed cells when these cells were stimulated with DNP-OA. These results suggested that DNP-specific T cells induced with DNP-Tbc selectively inhibited IgE antibody response.
Regulation of the Immune System by Synthetic Polynucleotides
Authors: Han Ihn H. , Johnson Arthur G.
Published: December 2022

Model systems for study of the action of adjuvants in immunodeficient states were developed in 10- to 14-day-old BALB/aj mice and aging BALB/aj mice (12 to 16 months). With sheep red blood cells as antigen polyadenylicpolyuridylic acid complexes (poly A:U) were found to be stimulatory in both the neonatal and aging mice. The effect of poly A:U was similar to that seen when 5 × 105 thymocytes from immunologically mature mice were given with antigen. Cell-free supernatant fluids induced by incubation of poly A:U with thymocytes likewise were capable of restoring the number of antibody-forming cells to normalcy in aging mice.
Receptor-Blocking Factor Present in Immune Serum Resembling Auto-Anti-Idiotype Antibody
Authors: Bankert Richard B. , Pressman David
Published: December 2022

Previous studies have shown that rabbit antibody-forming cells in the primary and secondary response possess cell-associated antigen-binding receptors. In the present study, we demonstrate that a factor appears in the serum of rabbits following immunization which inhibits the antigen binding of up to 60% of the receptor-bearing antibodyforming cells in both the primary and secondary response. These observations were made on lymph node cells from rabbits primed with either sheep red blood cells (SRBC)3 or 3-nitro-4-hydroxy-5-iodophenylacetic acid coupled to keyhole limpet hemocyanin (NIP-KLH). The inhibitory activity is not associated with anti-SRBC or anti-NIP antibody. In the primary response to SRBC, the antigen binding by day 6 antibody-forming cells is inhibited by the autologous days 7 to 10 inactivated and absorbed serum. In the secondary response to SRBC, the inhibitory factor peaks in the serum around day 10. Later, in both the primary and secondary immune response to SRBC, the inhibitory activity of the serum decreases rapidly. In the primary response to NIP-KLH, the inhibitory activity of the immune sera increased from day 7 through day 14.

The receptor-inhibiting factor is antigen specific since the serum from SRBC-primed rabbits inhibits SRBC binding by anti-SRBC antibody-forming cells, but it does not inhibit NIP binding by anti-NIP antibody-forming cells. Similarly, serum from NIP-KLH-primed rabbits inhibits NIP binding by anti-NIP antibody-forming cells, but does not inhibit the SRBC receptor on the anti-SRBC antibody-forming cells. The inhibition is not due to the presence of antihapten or anti-SRBC antibody competing with receptor sites, since the immune sera from one SRBC-primed animal inhibit antigen binding of its own antibody-forming cells, but do not inhibit the antigen binding of antibody-forming cells from other SRBC-primed rabbits.
Duodenal Immunoglobulin Deficiency in Graft Versus Host Disease (GVHD) Mice
Authors: Gold Jerome A. , Kosek Jon , Wanek Nancy , Baur Sonia
Published: December 2022

The small intestine is a well documented target organ in mouse and human GVHD, and diarrhea is a prominent part of the clinical GVHD syndrome. Although a plethora of systemic immune deficits has been documented in GVHD, the integrity of the small intestinal immune system has not been investigated. A correlation has not been demonstrated between systemic immune dysfunction and the incidence of lymphomas in mouse GVHD survivors. If gastrointestinal immune deficiency exists in mouse GVHD, its possible relationship to GVHD lymphomas, frequently abdominal, should be investigated.

GVHD was produced in newborn BLA (C57 BL/Ka females × BALB-C males) mice housed in a specific pathogen-free environment by the i.p. inoculation of 107 male BALB-C spleen cells. Control mice received syngeneic spleen cells. Twenty GVHD and 16 control mice were sacrificed at 3 weeks and specimens of duodenum were removed for routine histologic and immunofluorescent examination. All but one GVHD mouse (95%) had virtually absent duodenal IgA and IgM. Duodenal cellular fluorescence was demonstrated in all controls.

A significant duodenal immunoglobulin deficit has been demonstrated in 3-week-old GVHD mice. The relationship of this finding to GVHD diarrhea, wasting, and neoplasia remains to be determined.
Partial Regain of Activity in Heterologous Recombinants of Phosphorylcholine-Binding M-Components from Different Species
Authors: Riesen W. F.
Published: December 2022

Recombination experiments were performed with heavy and light chains derived from a Waldenström's IgM with specificity against phosphorylcholine. The recombinant molecules had an association constant for phosphorylcholine in the same order of magnitude as the native IgM; the number of binding sites at saturation was only slightly decreased in the reconstituted molecules, indicating regain of binding activity after recombination of IgM heavy and light chains. Heterologous recombinants obtained with polypeptide chains of another monoclonal IgM without demonstrable binding activity recovered only 5 to 10% of the binding activity of homologous recombinants. Hybrid molecules prepared with heavy and light chains from the phosphorylcholine-binding mouse IgA myeloma protein TEPC-15, however, regained as much as 41% of the binding activity of the homologous recombinants; these data suggest a considerable degree of structural homology shared by the human IgM and the murine IgA proteins with phosphorylcholine-binding specifity.
Immunoglobulin Binding by Mouse Intestinal Epithelial Cell Receptors
Authors: Guyer Ruth L. , Koshland Marian E. , Knopf Paul M.
Published: December 2022

The IgG receptors involved in transporting maternal antibodies to the blood stream of the young mouse were studied by feeding internally labeled mouse myeloma proteins and enzymatically generated specific fragments of these proteins. The data obtained from competition experiments showed the following: 1) intestinal receptors have a single specificity which is directed against IgG Fc determinants; 2) IgG subclass proteins differ in their affinities for the receptors and thus have similar but not identical Fc recognition sites; 3) the order of affinities of the IgG subclass proteins for the receptors correlates with the relative concentrations of the four subclass proteins in mouse milk; and 4) several subfractions of the Fc fragment were inactive in binding to the receptors. In many of their properties the intestinal receptors resemble the Fc receptors on other cell types, but they are apparently unique in their ability to bind tightly non-aggregated IgG molecules.
Enzymatic Degradation of Tumor Cells Damaged by Antibody Plus Complement
Authors: Reif Arnold E. , Robinson Cynthia M.
Published: December 2022

Rapid degradation of ascites tumor cells damaged by the action of antibody plus complement was found to be accomplished by all proteolytic enzymes active at physiologic pH that were tested. For three types of murine ascites tumor cells (Ehrlich ascites, sarcoma-180, and L1210 leukemia), this rate of degradation at low trypsin concentrations was proportional to a high power of enzyme concentration. This suggests that the simultaneous action of two or more enzyme molecules at adjacent cell surface sites is necessary. Cell degradation was assayed by determination of cell volume distribution with a Coulter multi-channel particle size analyzer. The present study may offer clues to in vivo mechanisms of cell degradation.
Inhibition by Rheumatoid Factor, Anti-Fc, and Staphylococcal Protein A of Antibody-Dependent Cell-Mediated Cytolysis against Herpes Simplex Virus-Infected Cells
Authors: Austin R. Marshall , Daniels Charles A.
Published: December 2022

Incubation of herpes simplex virus-infected human fibroblasts with the serum from a patient with herpes labialis rendered the cells susceptible to immune lysis by human mononuclear leukocytes (MNL) as well as complement. If, before the addition of MNL, the antibody-treated, infected monolayers were incubated with either IgM rheumatoid factor (RF), staphylococcal protein A (SPA), or anti-Fc γ serum, antibody-dependent cell-mediated cytolysis (ADCC) was markedly depressed. SPA and anti-Fc caused maximal inhibition (τ; 90%), whereas RF resulted in a 72% depression. The inhibition of ADCC was dependent on both the concentration of the Fc-reacting materials incubated with the antibody-coated target cells and the concentration of antiviral antibody incubated with the virus-infected fibroblasts. Experiments indicated that the Fc-reacting materials depressed ADCC at the target cell level by covering or altering Fc sites on cell-bound antiviral antibody.
Strain-, Age-, and Tumor-Dependent Distribution of Terminal Deoxynucleotidyl Transferase in Thymocytes of Mice
Authors: Pazmiño Nelson H. , Ihle James N.
Published: December 2022

The distribution of terminal deoxynucleotidyl transferase (TdT) peak I and peak II in thymuses and peripheral lymphoid tissues was examined in a variety of mouse strains in relation to tumor burden and age. TdT peak I was found to be present in all strains at comparable levels, which did not change with age. TdT peak II levels were also comparable for the strains examined at 1 week of age. In contrast to peak I, however, in NIH Swiss and AKR mice, peak II activity decreased rapidly at 2 weeks of age and by 6 weeks of age less than 2% of the initial activity remained. In C57BL/6 mice there was a similar loss of peak II activity with age although this change started at about 4 months of age and by 8 months of age approximately 15% of the initial activity remained. These changes did not appear to be due to the presence of an inhibitor.

Leukemic C57BL/6 and AKR mice were also examined for TdT. Both strains characteristically had TdT peak I in peripheral lymphoid tissues infiltrated with transformed thymocytes. AKR mice had only TdT peak I in the thymus, whereas C57BL/6 thymuses had both peak I and II at levels comparable to age-matched controls. No aberrant distribution of TdT was observed in a spontaneous reticulum cell sarcoma or Rauscher MuLV-induced erythroblastosis.
C3 Requirements for Formation of Alternative Pathway C5 Convertase
Authors: Daha Mohamed R. , Fearon Douglas T. , Austen K. Frank
Published: December 2022

Although alternative pathway C3 and C5 convertases both have active proteolytic sites dependent on the same protein, Bb, the quantitative requirements for the expression of these activities are sufficiently different to permit their delineation in terms of B input and cell-bound C3b. That the labile component of each active site is Bb was established by their parallel decay rates, regeneration of the original specificities with B in the presence of D̄, and stabilization of each convertase by C3NeF. The evidence that the spatial relationships of Bb and C3b on the cell surface for C3 and C5 convertase activities are distinct is based not only upon the decay and regeneration of each original convertase but more so upon their interconversion. C3 convertase is converted to C5 convertase by interaction with additional C3 whereas C5 convertase reverts to a C3 convertase by treatment with C3bINA. The capacity of C3bINA treatment to abolish C5 convertase sites without affecting C3 convertase sites indicates the existence of two functional species of C3b, one of which is protected in the C3bBb complex whereas the other is exposed.
In Vitro Activation of Mouse Macrophages by Rat Lymphocyte Mediators
Authors: Fidler Isaiah J. , Darnell John H. , Budmen Marilyn B.
Published: December 2022

Macrophage-activating factors (MAF)3 were released by presensitized rat lymphocytes stimulated in vitro with the appropriate antigens. Different supernatants of presensitized rat lymphocytes specifically stimulated in vitro with several different mouse, dog, and rat tumor or normal cells were capable of rendering normal rat and mouse macrophages nonspecifically cytotoxic in vitro to their respective syngeneic tumor cells. The release of active mediators by rat lymphocytes sensitized in vivo was dependent upon immunologically specific recognition of an antigen in vitro. When rat lymphocytes were incubated in vitro with antigens unrelated to the in vivo sensitizing antigens, no release of MAF occurred. Once rat MAF was released, it activated both syngeneic (rat) and xenogeneic (mouse) macrophages to kill tumor cells in vitro. These activated macrophages destroyed all syngeneic tumor targets. Such cytotoxicity was obtained even when the cells used to elicit release of MAF were totally unrelated to the target tumor cells. The data thus demonstrated that MAF can cross strain and even species specificities and can activate macrophages to kill tumors in a nonspecific manner. The cytotoxicity mediated by in vitro activated mouse macrophages decreased with time once the macrophages were removed from MAF; and by 7 days postactivation, the macrophages were not cytotoxic. However, when incubated again with MAF, significant reactivation was observed. This suggested that activation of macrophages in vivo may be a continuous process of lymphocyte-macrophage interaction.
A Homologue of the Rabbit κ-Chain Allotype b9 on IgG from a Cottontail Rabbit
Authors: Tosi Simonetta Landucci , Mage Rose G. , Tosi Roberto M.
Published: December 2022

Eight out of 12 anti-b9 antisera tested strongly bound 125IgG of only one of four individual cottontail rabbits (Sylvilagus floridanus). In addition to this apparent polymorphism of a b9 homologue in cottontail rabbits, a polymorphism defined by some anti-b5 antisera was found. Three of 15 anti-b5 antisera reacted with IgG from only two of the four cottontail rabbits. Reactions with anti-b4 and anti-b6 were similar to those with hare IgG. Most anti-b4 and anti-b6 antisera bound the IgG from each animal. The cottontails we tested also resembled the hare with respect to their weak reactivity with some anti-a2 antisera (VH allotype) and strong reactivity with anti-15 (an allotype localized in the Fc portion of rabbit γ-chains).
Immune Response of the Mouse to the Major Core Protein (p30) of Ecotropic Leukemia Viruses
Authors: Nowinski Robert C. , Watson Andrew
Published: December 2022

Sera from normal C57BL/6 mice contained low titers of antibodies against proteins of MuLV. Sera from C57BL/6 mice that were immunized with allogeneic leukemia cells sometimes contained high-titered antibodies against the p15 protein of MuLV; these antibodies detected groupspecific antigenic determinants of the p15 protein, since reactions were observed with the p15 proteins of both AKR and Moloney viruses. In contrast, antisera prepared in C57BL/6 mice against the AKR leukemia K36 reacted strongly with the p30 protein of MuLV, as well as with p15. Antibodies in the C57BL/6 anti-AKR K36 sera detected group-specific antigenic determinants of the p30 protein; reactions were observed with the C57BL/6 anti-AKR K36 serum and the p30 proteins of both AKR and Moloney viruses. It was concluded that mice do have the capacity to respond immunologically to antigenic determinants of the MuLV p30 protein, although in most circumstances this is not observed.
Soluble Antigens and Antibodies in Sera from Baboons Infected with Schistosoma mansoni
Authors: Houba Vaclav , Koech Davy K. , Sturrock Robert F. , Butterworth Anthony E. , Kusel John R. , Mahmoud Adel A. F.
Published: December 2022

Sera from baboons (Papio anubis) exposed percutaneously to S. mansoni cercariae were examined for the presence of antigens and antibodies at different times after infection by counter-current immunoelectrophoresis. The first antigens detected were gut-associated antigens (2 to 4 weeks after infection) followed by membrane antigens (3 to 5 weeks) and soluble egg antigens (7 weeks). Corresponding antibodies were detected 1 to 2 weeks later. The possibility that the simultaneous detection of both components in serum strongly suggests the presence of circulating immune complexes is discussed.
Intestinal Uptake of Macromolecules
Authors: Allan Walker W. , Abel Stephen N. , Wu Margaret , Bloch Kurt J.
Published: December 2022

The in vitro absorption by rat jejunal and ileal gut sacs of soluble antigen-antibody complexes and of antigen alone was compared. Complexes prepared in 2-fold antibody excess were absorbed in significantly smaller quantities than was antigen alone. Complexes prepared in 50-fold antigen excess were absorbed by jejunal gut sacs in quantities equivalent to that of antigen alone, whereas the absorption of such complexes by ileal sacs was somewhat decreased compared to that of antigen. There was less radiolabeled antigen tightly bound to the intestinal mucosa of gut sacs exposed to complexes prepared in antigen or antibody excess compared to antigen alone. Complexes prepared in antibody excess appeared to stimulate secretion of mucus and complexes were associated with the mucus fraction. It was suggested that the large size of complexes prepared in antibody excess may result in their trapping in the mucus coat of the gut, thereby preventing contact with the surface of the enterocyte from whence uptake by pinocytosis is initiated. In addition, complexes appear to be shed from the surface with mucus by a mechanism still to be elucidated.
Separation of Slow Reacting Substance of Anaphylaxis (SRS-A) from Human Lung Into Four Biologically Active Fractions
Authors: Takahashi Hidenobu , Webster Marion E. , Newball Harold H.
Published: December 2022

Slow reacting substance of anaphylaxis (SRS-A) was released from human lung passively sensitized with ragweed antibody and challenged with specific antigen E. After purification by ethanol extraction, incubation with alkali (0.1 M NaOH for 30 min at 37°C) and chromatography on silicic acid and DEAE-cellulose, human SRS-A was separated into four biologically active fractions (Fractions I to IV). Arylsulfatase (Type H-1) in 0.1 M sodium acetate buffer, pH 4.5, destroyed the biologic activity of only Fraction I. All four fractions, like SO4-, inhibited the arylsulfatase activity at pH 4.5 but not at pH 6.0 when p-nitrocatechol sulfate was used as substrate. These results suggest that SRS-A contain a sulfur group and that human SRS-A, like the prostaglandins, may be a family of compounds. The instability of the purified SRS-A to storage remains a major barrier to their further purification and chemical identification.
A Human Cold Agglutinin Which Binds Lacto-N-NeoTetraose
Authors: Tsai Chao-Ming , Zopf David A. , Wistar Richard , Ginsburg Victor
Published: December 2022

A human cold agglutinin (McC) has been isolated from the serum of a patient with Waldenström's macroglobulinemia by affinity chromatography with a column of glutaraldehyde-fixed erythrocyte stroma mixed with celite. The agglutinin, which is an IgM κ, reacts weakly with normal adult erythrocytes and strongly with cord cells as well as with adult Oh and Ol cells. The reactivity of all cell types tested was increased to approximately the same level by treatment of the cells with ficin. Inhibition studies indicate the agglutinin is specific for the nonreducing terminal carbohydrate sequence Galβ1-4GlcNAcβ1-3Gal….
Ability of H-2 Regions to Induce Graft-vs-Host Disease
Authors: Klein Jan , Chiang Chin Lee
Published: December 2022

Individual young adult F1 hybrid mice were irradiated with 500 R and 24 hr later injected with 5 × 107 spleen cells obtained from a sex-matched parental-strain donor. The injected animals were then followed for a period of 3 months and loss of body weight, mortality rate, and other signs of fatal graft-vs-host disease (GVHD) were recorded. The donor-recipient strain combinations were selected in such a way as to provide genetic differences in the entire H-2 complex, the K or D regions alone, the K or the D end, and the central (I) regions alone. The data obtained on only few combinations indicate that strong GVHD (100% mortality rate within the first month after the injection) occurs only in those donor-recipient combinations which differ in the entire H-2 complex or in the K end (K + I regions). Much weaker GVHD (mortality rate of only 50% or less and death of individual mice spread over the entire observation period) is observed when the donor and the host differ in either the K, I, or D region alone. The degree of GVHD induced by three regions, when taken singularly, is about the same. Surprisingly, the K-region GVHD was somewhat stronger in combinations of mutant strains in comparison with recombinant-strain combinations.
A New Activity of Complement Component C3: Cell-Bound C3b Potentiates Lysis of Erythrocytes by C5b,6 and Terminal Components
Authors: Hammer Carl H. , Abramovitz Aaron S. , Mayer Manfred M.
Published: December 2022

EAC4b,3b (sheep erythrocytes carrying rabbit antibody and guinea pig complement component fragments C4b and C3) adsorb human C5b,6 reversibly; the avidity of binding varies inversely with ionic strength. We believe that the receptor of C5b,6 is contributed by the cell-bound C3b because the binding capacity of EAC4b,3b varies with C3b multiplicity and can be blocked with rabbit antibody to guinea pig C3. The fixation of C5b,6 to the erythrocyte-bound C3b serves to concentrate C5b,6 on the cell surface; as a consequence, the hemolytic efficiency of C5b,6 is almost 100 times greater when assayed with EAC4b,3b than with plain erythrocytes. This potentiation represents a hitherto unrecognized function of cell-bound C3b.
Influenza A Virus Interaction with Murine Lymphocytes
Authors: Woodruff Judith J. , Woodruff Jack F.
Published: December 2022

The effect of influenza virus A/Japan 305 (H2N2) on the path of migration of recirculating lymphocytes has been studied. 51Cr-labeled rat thoracic duct lymphocytes (TDL) were incubated with virus at 37°C for 1 hr and then infused i.v. into syngeneic recipients which were killed 1 hr later. Virus-treated TDL accumulated in the liver and their recovery in lymph nodes and spleen was severely reduced. Changes in lymphocytes induced by virus developed rapidly and were evident after incubation for only 15 min. UV-irradiated virus altered the pattern of lymphocyte localization but attachment of heat-inactivated virus to lymphocytes in vitro had no effect on their distribution in vivo. Evidence was obtained that some virus-treated TDL, initially sequestered in the liver, subsequently recovered their ability to circulate normally. Recovery was not complete and a population of cells failed to regain their ability to home into lymph nodes. Evidence is also presented demonstrating that influenza virus affected the homing properties of both T and B cells. It is suggested that aberrations in lymphocyte homing were mediated by the viral neuraminidase which induces changes in the cell membrane leading to their accumulation in the liver.
Appearance of Functional Lymphocytes in Fetal Liver
Authors: Phillips R. A. , Melchers F.
Published: December 2022

During ontogeny of the mouse, cells bearing surface Ig first appear at approximately 16 days of gestation. To characterize B cell differentiation during embryogenesis further, we have measured several functional activities of B cells and their precursors. B cell function was measured in two assays, response to sheep red blood cells in a transplantation assay, and response in vitro to a B cell mitogen. By both assays, B function is first detectable at 16 days, the same time that Ig-positive cells appear. The immediate precursors of B cells, PB cells,3 can also be measured by a transplantation assay. This activity is first detectable in fetal liver at 13 days. The yolk sac at 13 days does not contain significant PB activity even though both fetal liver and yolk sac contain pluripotent stem cells, spleen colony-forming units, at that time. These data are consistent with the hypothesis that the development of B lymphocytes occurrs early in ontogeny and that the fetal liver may provide the inductive stimulus for B cell maturation.
Hypergammaglobulinemia in Chickens Congenitally Infected with an Avian Leukosis Virus
Authors: Qualtiere Louis F. , Meyers Paul
Published: December 2022

Significantly elevated (2- to 5-fold higher than controls) serum levels of IgG were found in chickens congenitally infected with F42 strain of avian leukosis (ALV-F42), a subgroup A avian leukosis virus (ALV). A further increase in IgG levels in congentially infected birds was found to be induced by injection of influenza virus in complete Freund's adjuvant (CFA). Serum immunoglobulin M (IgM) levels were not significantly elevated in ALV congenitally infected chickens except in those animals that had been injected with influenza virus in CFA. Hypergammaglobulinemia in ALV infected birds resulted only after congenital infection and not after infection of immunologically competent birds. Therefore this phenonemen appeared to have striking parallels with other persistent or chronic viral infections that have been previously described in mammals.
The Metabolism of IgE
Authors: Waldmann Thomas A. , Iio Atsushi , Ogawa Makio , McIntyre O. Ross , Strober Warren
Published: December 2022

IgE metabolic turnover studies with purified radioiodinated IgE were performed in normal individuals and in a patient with IgE myeloma. The validity of the turnover studies was established in several ways, including comparisons of radioiodinated IgE turnover with the turnover of endogenously labeled 14C-IgE and with the turnover of infused unlabeled IgE in a patient with hypogammaglobulinemia.

The geometric mean serum IgE concentration in 73 normal adults was 96 ng/ml with a 68% confidence interval of 24 to 386 ng/ml. Metabolic turnover studies in 10 control individuals disclosed a geometric mean total circulating IgE of 4.1 µg/kg, a mean percentage of the total exchangeable IgE in the intravascular space of 41%, a mean half-time of survival of IgE of 2.7 days, a mean fractional catabolic rate of 94% of intravascular pool per day, and a geometric mean synthetic rate of 3.8 µg/kg/day. IgE has the lowest synthetic rate and highest fractional catabolic rate of the five major classes of immunoglobulin molecules.

In contrast to these normal values, a patient with IgE myeloma had a serum IgE concentration of 42 mg/ml, a total circulating IgE of 1.7 g/kg, and a synthetic rate of 270 mg/kg/day. Furthermore, although the synthetic rate was vastly increased, the survival time was prolonged and the fractional catabolic rate was decreased to 5.1 days and 16 to 22% of the intravascular pool per day, respectively.

These data are compatible with the concept that IgE is catabolized in part by a mechanism common to all immunoglobulin classes and in part by a unique mechanism not available to other immunoglobulins. At very high IgE serum concentrations, such as those encountered in patients with IgE myeloma, the unique mechanism would be saturated and only the catabolic pathways available to all immunoglobulins would be available to IgE.
Perturbation of Lymphocyte Circulation in Experimental Murine Leprosy
Authors: Bullock Ward E.
Published: December 2022

Infection of Lewis rats with Mycobacterium lepraemurium is characterized by granulomatous pathology primarily involving the paracortical areas of lymph nodes and periarteriolar lymphocyte sheaths of the splenic white pulp. Intravenous infusion of radiolabeled thoracic duct lymphocytes (TDL)2 from normal syngeneic donors failed to produce a significant increase of cell output and radioactivity in the thoracic duct lymph of infected rats as compared with a marked increase in matched control recipients. Conversely, the migration of TDL from infected donor rats was normal in uninfected control rats that had been infused with serum from infected donors.

The onset of the lymphocyte traffic disturbance takes place between 2 and 6 weeks after inoculation of viable M. lepraemurium. However, inoculation of heat-killed organisms produces little perturbation of lymphocyte circulation. Thus, the abnormal circulation of TDL in rats with active infection appears to be secondary to granulomatous pathology in lymphoid organs that disturbs cell traffic through these organs.
Perturbation of Lymphocyte Circulation in Experimental Murine Leprosy
Authors: Bullock Ward E.
Published: December 2022

Intravenous infusion of radiolabeled thoracic duct lymphocytes (TDL)2 from normal syngeneic donors to rats experimentally infected with Mycobacterium lepraemurium fails to produce a significant increase of cell output and radioactivity within the thoracic duct lymph. Conversely, there is a marked increase in cell counts and radioactivity in the thoracic duct lymph of control recipients.

Splenectomy of infected rats prior to the infusion significantly increased the output of cells and radioactivity from the TD of these rats although it was not restored to normal. Serial quantitation of radioactivity in lymphoid organs of infected rats after infusion of 51Cr-labeled TDL revealed significantly increased uptake by the spleen as compared with the spleens of controls. Thus, the spleen of infected rats was a major trap for recirculating TDL. TDL were also trapped to a lesser extent by the lymph nodes and liver of infected rats.

The circulation of TDL was not disturbed significantly in control rats with massive splenomegaly and red pulp hyperactivity induced by i.p. injection of methyl cellulose. Since murine leprosy preferentially involves the periarteriolar lymphocyte sheaths of the splenic white pulp and paracortical area of lymph nodes, it is suggested that the disturbance of lymphocyte circulation is secondary to pathology within these areas.
Differences in Ultrastructural Appearance and Modulation of Endogenous and Exogenous Surface Immunoglobulin of Rabbit Lymphocytes
Authors: Linthicum D. Scott , Bahu Raja M. , Sell Stewart
Published: December 2022

Endogenous and exogenous surface Ig (sIg)3 of rabbit peripheral blood lymphocytes (PBLs) differ in ultrastructural appearance and modulation characteristics. Endogenous sIg occurs as small sessile patches on 70% of freshly prepared PBLs after specific mixed anti-globulin immunoferritin labeling. These patches are closely associated with the surface membrane and readily undergo endocytosis when labeled cells are warmed to 37°C. The binding of exogenous Ig may be demonstrated by exposure of PBLs to normal allogenic or xenogenic serum in vitro. Aggregated IgG is responsible for the majority of the serum Ig binding; deaggregated IgG binds poorly and Fab′ fragments of IgG do not bind. Exogenous Ig exists as large aggregates precariously attached to the cell surface on approximately 70% of the PBLs which do not undergo endocytosis when warmed to 37°C but appear to be shed or sloughed from the cell surface. We conclude a) that most rabbit PBLs have both endogenous surface Ig and Fc receptors for aggregates of IgG; b) that endogenous and exogenous sIg can be differentiated by ultrastructural features; c) that exogenous sIg is not detectable on freshly prepared PBLs unless incubated in vitro with aggregated Ig; and d) the exogenous sIg may not have a functional role in lymphocyte activation.
A Galactose-Inhibitable Mitogen for Human Lymphocytes from the Sponge Axinella Polypoides
Authors: Phillips Stephanie Gordon , Bretting Hagen , Kabat Elvin A.
Published: December 2022

Of two galactose-binding hemagglutinins isolated from the sponge Axinella polypoides, axinella I was strongly mitogenic for human peripheral blood lymphocytes, and axinella II was not. Purified T cells responded strongly and B cells weakly to axinella I. Mitogenic response, as monitored by rate of 3H-thymidine incorporation on the third day of culture, was specifically inhibited by Dgalactose, Dfucose, raffinose, or 2-deoxy-D-galactose added within 5 hr of the mitogen. Mitogenic response was correlated with degree of lymphocyte agglutination. The effectiveness of a given sugar in inhibiting mitogenic response to axinella I paralleled its potency in inhibiting precipitation of lectin by blood group substances. If an inhibitory concentration of Dgalactose was added 24 to 40 hr after mitogenic activation, rate of 3H-thymidine uptake at 72 hr was two to twenty times above the rate induced in cultures to which no galactose was added. Dgalactose at a subinhibitory concentration (10 µg/ml) enhanced 3H-thymidine incorporation. Axinella I depressed 3H-thymidine incorporation induced by phytohemagglutinin or Con A, an effect reversible by Dgalactose. These findings suggest that axinella I has two antagonistic effects on human lymphocytes: a) mitogenic activation and b) depressive activity resulting from depletion of essential galactose moieties.
Characterization of Ia8 Antigen, Thy-1.2 Antigen, Complement Receptors, and Virus Production in a Group of Murine Virus-Induced Leukemia Cell Lines
Authors: Chesebro Bruce , Wehrly Kathy , Chesebro Kevin , Portis John
Published: December 2022

Ia8, a cell membrane antigen controlled by gene(s) located in the I region of the H-2 complex, was found on 9 of 26 murine leukemia cell lines. In addition, 3 of the 9 Ia8-bearing lines had a membrane receptor for antigen-antibody-complement complexes. Six of 26 lines bore the Thy-1.2 antigen. Ia8 and Thy-1.2 antigens were mutually exclusive on the cell lines studied. The strain of virus used to induce the leukemia, the H-2 type of the cells, and the techniques of leukemia cell propagation all appeared to influence the antigenic characteristics of the cell lines obtained. Production of infectious murine leukemia virus in vitro and expression of leukemia virus-induced membrane antigens did not appear to correlate with the presence of Ia8 or Thy-1.2 antigens or with the H-2 type of the cells.
Maturation of B Lymphocytes in Rats
Authors: Strober Samuel
Published: December 2022

We examined the ability of large and small thoracic duct cells obtained from Lewis rats primed to DNP to restore the adoptive secondary anti-DNP response in irradiated syngeneic hosts given an excess of T helper cells. The large cells were four to five times more active on a per cell basis than were the small cells. However, the large cells constitute only 7 to 8% of the thoracic duct cells and, therefore, make a minor contribution to the restorative activity of the unfractionated cells.

Pretreatment of thoracic duct cell donors with high specific activity 3H-TdR for 48 hr before cannulation markedly reduced the memory B cell activity of the large cells, but had little effect on that of small cells. In addition, the activity of the large cells diminished with time after primary immunization, but that of the small cells remained stable. Immunofluorescent staining of the large and small cells for surface IgM and IgG, and subsequent sorting on the fluorescence-activated cell sorter (FA CS), showed that surface IgM was present on large memory B cells, and that IgG was present on small memory B cells. The experimental results suggest that two subpopulations of memory B cells in the thoracic duct lymph differ by size, rate of turnover, persistence after primary immunization, and class of surface IgG.
Nucleoside Specificity in the Carrier IgG-Dependent Induction of Tolerance
Authors: Stollar B. David , Borel Yves
Published: December 2022

Induction of tolerance to nucleoside haptens in BALB/c mice with isologous IgG conjugates bearing four nucleosides simultaneously (A,G,C,T)-IgG was confirmed. A mixture of separate nucleoside-IgG tolerogens (A-IgG, G-IgG, C-IgG, and T-IgG) was as effective or more effective than the (A,G,C,T)-IgG form in suppressing the response to (A,G,C,T)-KLH. The nucleosides acted independently and simultaneously, since tolerogens with varying combinations of nucleosides caused specific suppression of the respones to only those nucleosides present on the tolerogen. Nucleoside-IgG conjugates did not suppress the response to denatured DNA-methylated bovine serum albumin, in which larger oligonucleotide determinants predominate. In varying combinations, guanosine was the dominant nucleoside both for immunization and for induction of tolerance. After three or four immunizations, control immunized animals made mainly IgG anti-nucleoside antibodies and this IgG antibody formation was preferentially suppressed in tolerogen-treated animals. Tolerance could be established before the primary or secondary immunization and it then persisted for at least 75 days through a fourth course of immunization. The same dosage of tolerogen did not reverse a strongly established anti-nucleoside antibody production after a tertiary response.
Release of Chemical Mediators from Partially Purified Human Lung Mast Cells
Authors: Paterson Nigel A. M. , Wasserman Stephen I. , Said Jonathan W. , Austen K. Frank
Published: December 2022

Human lung mast cells dispersed by enzymatic digestion of human lung fragments were concentrated to greater than 50% purity by sedimentation in isopycnic and velocity gradients. The dispersed lung mast cells had a characteristic ultrastructural appearance including granules with a scroll or reticular structure surrounded by perigranular membranes. Histamine and preformed eosinophilotactic activity sedimented with the mast cells on isopycnic gradients, and the mast cells and these mediators were separated from the bulk of the other lung cells after velocity gradient sedimentation. The histamine content of isolated lung mast cells was calculated to range from 1.0 to 5.5 pg/cell. The quantity of SRS-A generated with anti-IgE or specific antigen was relatively limited but confined to the mast cell-rich fractions and associated with the release of histamine and eosinophilotactic activity.
In Vitro Responses of CBA/N Mice: Spleen Cells of Mice with an X-Linked Defect that Precludes Immune Responses to Several Thymus-Independent Antigens Can Respond to TNP-Lipopolysaccharide
Authors: Mosier D. E. , Scher I. , Paul W. E.
Published: December 2022

Spleen cells from CBA/N mice with an X-linked B cell defect were examined for their ability to form antibody in vitro after stimulation with the T-independent antigen TNP-LPS. In contradistinction to their failure to respond to some conventional T-independent antigens such as type III pneumococcal polysaccharide or DNP-AECM-Ficoll, spleen cells from (CBA/N × DBA/2)F1 male mice were able to make a specific anti-TNP PFC response after culture with TNP-LPS. Their response differed from that of phenotypically normal (CBA/N × DBA/2)F1 female litermate spleen cells in that more TNP-LPS was required to elicit the peak anti-TNP response and the anti-TNP antibody secreted by F1 male cells was of lower avidity than that of F1 female cells. The polyclonal antibody response to unsubstituted LPS did not differ substantially between normal and defective B cells. Thymus-derived cells were not required for the TNP-LPS response by either F1 male or female cells. We conclude that CBA/N B cells can respond to certain T-independent antigens that are able either to induce a very strong activating signal upon ligand-surface receptor interaction and/or to stimulate immature B cells (with a characteristic high surface immunoglobulin profile) which fail to respond to antigens like DNP-AECM-Ficoll.
Regulatory Effect of Interferon on T Cells in Vitro
Authors: Heron Iver , Berg Kurt , Cantell Kari
Published: December 2022

Purified human lymphocyte interferon (PIF) was added to mixed lymphocyte cultures; DNA synthesis was measured and killer-cell generation was determined. At certain concentrations, PIF inhibited proliferation, but at the same time increased the killer efficiency of the resultant culture cells. It is suggested that lymphokines, apart from their normal mediator function, may play a role as regulators of the generating immune response.
Solubilization of IgA Immune Precipitates by Complement
Authors: Miller Gary W.
Published: December 2022

The complement (C) system can solubilize immune precipitates prepared with antibodies of the IgG class, and apparently also of the IgM class. This paper shows that C can also solubilize immune precipitates prepared with two different antigen-binding IgA myeloma proteins. Immune precipitates were prepared with a) mouse myeloma protein TEPC 15 and PC-KLH, and b) mouse myeloma protein MOPC 315 and DNP-BSA. The precipitates could be solubilized by fresh mouse serum, but not by zymosan- or heat-inactivated serum. The rate of solubilization was not affected by the removal of Ca++ ions. These results verify that the C-mediated solubilization effect can proceed entirely via the alternative C pathway, and lend increased support to the view that the effect is a general phenomenon, not restricted to a particular antibody class or type of antigen.
Comparison of the Inactivation of IgM and IgG Complement Fixation Sites by Acid and Base
Authors: Stollar B. David , Stadecker Miguel J. , Morecki Shoshana
Published: December 2022

Rabbit IgM antibodies to denatured mammalian or T6 bacteriophage DNA or poly(A)·poly(U) irreversibly lost complement-(C) fixation reactivity on exposure to low pH and reneutralization, with a halving of the complement-fixation titer occurring after treatment at about pH 3. The titers of IgG antibodies to denatured phage DNA, to poly(A)·poly(U), or to hemocyanin were halved only after exposure to pH 2. Inactivation by acid was enhanced by low protein concentrations, incubation at higher temperatures, and by slow reneutralization; under all these conditions it was more extensive with IgM than with IgG. Inactivation of IgM C-fixation activity at pH 2.5 and room temperature was a first order reaction, with a half-time of about 20 min. Both classes retained antigen-binding activity after exposure to pH 2. In the alkaline range, full C-fixation reactivity was retained by both classes after reneutralization from pH 11.5, some loss occurred at pH 12, and total irreversible inactivation occurred by pH 12.5. In the latter case, antigen-binding activity was also lost. The C-fixation inactivation curves in the alkaline range were similar for IgG and IgM antibodies.
Characterization of Antibodies to the Structural Polypeptides of HBsAg: Evidence for Subtype-Specific Determinants
Authors: Gold Jon W. M. , Shih J. Wai-Kuo , Purcell Robert H. , Gerin John L.
Published: December 2022

Antisera prepared in guinea pigs to the structural polypeptides of HBsAg/adw and HBsAg/ayw were examined by a modified passive hemagglutination assay for antibodies to the subtype-specific d and y determinants. All of the isolated polypeptide fractions stimulated antibodies to both group-specific and subtype-specific antigens of the native HBsAg particle from which they were derived. These data indicate that the polypeptides have similarities in their immunochemical structure.