bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-Lasting in Vitro Immune Response to a Distinct Antigenic Determinant of a Bacterial Protein
Authors: Macario Alberto J. L. , de Macario Everly Conway
Published: December 2022

Long-lasting (60 days or more) antibody responses in vitro by rabbit lymph node fragments to a distinct determinant of Escherichia coli β-D-galactosidase were obtained by supplementing culture medium with fetal calf and horse serum. Antibodies released in the supernatant were removed every 3rd to 5th day together with the spent medium, without pooling to minimize intermixing of molecules synthesized far apart in time. Antibody titer, association constant, and heterogeneity index were measured in medium samples collected throughout the response in order to draw profiles of their changes under conditions whereby a limited number of clones synthesize antibodies in a closed system without connection to antigen depots, central lymphoid organs, and circulating cell and antibody pools. It was found that antibody affinity changes cyclically and that such cycles may be repeated. Cycles are composed of an ascendant limb with a gradual increase in affinity and a parallel diminution of heterogeneity. A descendant limb follows with the opposite modifications. High affinity antibodies predominate at the peak of the cycles, whereas low affinity molecules take over at the end of the cycles until the next ascendant limb begins; these persist after the last cycle has waned.
Lymphokine Production by C3b-Stimulated B Cells
Authors: Sandberg Ann L. , Wahl Sharon M. , Mergenhagen Stephan E.
Published: December 2022

Trypsin cleavage of guinea pig C3 (60 sec, 20°C) yields a fragment which stimulates guinea pig lymphocytes to produce a chemotactic lymphokine. These digested C3 preparations possess only minimal inherent chemotactic properties. The response is completely inhibited by prior adsorption of the trypsin-derived C3 fragments with insolubilized anti-C3. The active C3 fragment is C3b as demonstrated by the elution of activity in the exclusion volume of Sephadex G-75 (m.w. > 50,000 daltons). The C3b-dependent cellular-derived chemotactic factor is present in the supernatants of B cell cultures and totally absent in those of T cell cultures. Generation of this lymphokine occurs in the absence of cellular proliferation.
Thymus-Repopulating Capacity of Cells that Can be Induced to Differentiate to T Cells in Vitro
Authors: Komuro Katsutoshi , Goldstein Gideon , Boyse Edward A.
Published: December 2022

It was established previously that committed precursors of T cells, which reside in bone marrow and spleen and lack T cell surface differentiation antigens, can be induced by thymopoietin and certain other agents to differentiate rapidly in vitro into T cells bearing typical surface antigens, including Thy-1 and TL (Komuro-Boyse assay). To relate this differentiative step observed in vitro to physiologic events in vivo, a system was devised to trace the migration of precursor cells to the thymus, and their maturation to T cells.

Lethally irradiated mice of a TL- strain received spleen cells from TL+ hybrids i.v., and the TL+ population of the thymus was enumerated 13 to 20 days later. Donor TL+ cells first became detectable at 13 days and increased thereafter. Preliminary tests showed that cells capable of migrating to the thymus have a similar density to the cells that are inducible in the Komuro-Boyse assay, this being lower than that of mature of T cells.

The thymus-repopulating properties of the donor spleen population were not affected by: 1) pre-treatment in vitro with thymus extract or thymopoietin, which initiates differentiation of T cells precursors, nor b) pre-treatment with anti Thy-1 serum plus complement, which eliminates differentiated T cells. But pre-treatment a) and b) applied in sequence markedly reduced the capacity of spleen cells to repopulate the thymus.

These results can be interpreted as follows: induction of Thy-1-TL- precursor cells (pro-thymocyte) in vitro yields Thy-1+TL+ cells (early thymocytes) which have not yet lost their property of repopulating the thymus; therefore, thymus-repopulation was not depleted by treatment a) alone, which induced Thy-1+TL+ cells, nor by treatment b) alone, which did not affect thymus-repopulation by Thy-1-TL- cells, although treatments a) plus b) did eliminate the newly induced Thy-1+TL+ cells and thus impaired repopulation of the thymus.

We conclude that the cell which responds to thymopoietin in the Komuro-Boyse assay by expressing the T cell surface phenotype is the same cell (pro-thymocyte) that normally migrates in vivo from hemopoietic tissues to the thymus and is there induced by thymopoietin to express the phenotype of an early T cell.
Relation of Structure to Function in Bacterial Endotoxins
Authors: Nowotny Alois , Behling Ulrich H. , Chang Helena L.
Published: December 2022

This is the first report describing in vivo biologic activities elicited by a non-toxic, polysaccharide-rich, water soluble fraction obtained by partial acidic hydrolysis from endotoxic lipopolysaccharide. The two activities present in this preparation were a) mouse bone marrow cell colony formation stimulation (CSF) and b) protection of mice against lethal irradiation. With polysaccharide-deficient rough mutants of Salmonella minnesota, the CSF-inducing activity could be restricted to the “core” region of the LPS structure. Sixty-minute hydrolysis with 1 N HCl at 100°C or 0.1 M sodium metaperiodate oxidation at cold room temperature completely abolished CSF-inducing activity of the preparation, whereas it showed considerable resistance to mild alkaline hydrolysis. These findings indicate that the active component in this preparation is carbohydrate in nature.

Lipid preparations from smooth LPS or from Re rough mutants are either much less active or completely inactive in the above two assays. The fully active polysaccharide-rich preparation was found to be inert in seven other characteristic endotoxicity parameters.
Syngeneic Adoptive Immunotherapy and Chemoimmuno-therapy of a Friend Leukemia: Requirement for T cells
Authors: Berenson James R. , Einstein Albert B. , Fefer Alexander
Published: December 2022

The aim of the study was to determine which cell mediates adoptive immunotherapy and chemoimmunotherapy of a syngeneic transplantable Friend virus-induced leukemia (FBL-3). An adoptive immunotherapy model was developed in which adult C57BL/6 mice given a lethal dose (104) of FBL-3 on day 0 were saved by treatment on day 1 with C57BL/6 spleen cells or peritoneal exudate cells (PEC) immune to FBL-3. Cells passed through a nylon wool column to remove B cells and macrophages or treated with carbonyl iron to remove phagocytic cells remained effective, whereas cells treated with anti-ϑ serum and complement were far less effective. For adoptive chemoimmunotherapy, mice inoculated with 107 FBL-3 were treated 5 days later with cyclophosphamide (CY) plus immune spleen cells. CY, with or without non-immune cells, prolonged survival but all mice died with leukemia, whereas mice given CY plus immune cells survived tumor-free. As an adjunct to CY, immune cells passed through nylon wool or treated with carbonyl iron remained quite effective whereas cells treated with anti-ϑ serum and complement were far less effective. Thus, immune thymus-derived lymphocytes were required for the adoptive immunotherapy of an early leukemia or chemoimmunotherapy of a disseminated leukemia.
Identification of the Cell Population Involved in Viral-Specific Cell-Mediated Cytotoxicity in Man: Evidence for T Cell Specificity
Authors: Rola-Pleszczynski Marek , Hurtado Rodrigo C. , Woody James N. , Sell Kenneth W. , Vincent Monroe M. , Hensen Sally A. , Bellanti Joseph A.
Published: December 2022

The nature of the cell population involved in lymphocyte-mediated cytotoxicity to baby-hamster-kidney (BHK-21) target cells persistently infected with rubella virus was investigated by a 51Cr-release microassay. After depletion of the T cell population with an antiserum to human-thymus-lymphoid tissue antigen (HTLA), the purified B cell population showed a decrease in E-rosette formation (9.0 ± 2.2% compared to 69.6 ± 9.1% before treatment) and an insignificant degree of cytotoxic activity against rubella-infected target cells (specific immune release of 51Cr was 0.9 ± 2.6% compared to 24.2 ± 3.8 before treatment). A purified T cell population, prepared by depletion of B cells with an anti-human immunoglobulin serum and complement, was found to show no alteration in E-rosette formation (85.2 ± 6.2%) or cytotoxicity (30.3 ± 4.4% SIR) but showed decreased EA- and EAC-rosette formation (2.7 ± 1.5% and 10.5 ± 3.2%, respectively, compared to 19.4 ± 2.9% and 28.0 ± 4.1% before treatment). A monocyte-depleted population prepared by removal of the plastic adherent mononuclear cells showed no significant alteration of rosette formation or cytotoxicity.

These experiments suggest that the predominant lymphoid population responsible for direct cell-mediated cytotoxicity to virus infected target cells in the 51Cr-release microassay appears to be effected by a thymus-dependent lymphocyte population.
Enhanced Destruction of Lymphoid Cell Lines by Peripheral Blood Leukocytes Taken from Patients with Acute Infectious Mononucleosis
Authors: Hutt Lindsey M. , Huang Yung Tsun , Dascomb Harry E. , Pagano Joseph S.
Published: December 2022

The cytotoxicity of peripheral blood leukocytes from normal human donors and from patients with EBV-as-sociated infectious mononucleosis (IM) has been determined for human lymphoid cell lines (LCL) containing Epstein-Barr virus (EBV) DNA. In a 51Cr release assay, mononuclear leukocytes from all donors are spontaneously cytotoxic. Leukocytes taken from patients within the first 2 weeks of overt IM are significantly more cytotoxic. This increased cytotoxicity declines to the spontaneous level as the disease progresses. The increase shows no correlation with the degree of lymphocytosis but a positive correlation with numbers of circulating atypical cells. The reaction is apparently not directed against histocompatability antigens, known EBV membrane antigens, or other characteristics of fresh human lymphoid cells. Susceptibility to damage is shared by bone marrow-derived (B) cell lines but not thymus derived (T) cell lines. EBV-gene products cannot be solely responsible for expression of the unknown characteristic. Transformation of B cells with EBV in vivo or in vitro, however, may trigger its expression.
Antibody-Dependent Cell-Mediated Cytotoxicity in Humans
Authors: Trinchieri Giorgio , de Marchi Mario
Published: December 2022

Antibody-dependent cytotoxicity mediated by human peripheral lymphocytes is an active energy-requiring phenomenon. In this study the relative importance of glycolysis and respiration was analyzed, by measuring the effect of various metabolic inhibitors (sodium azide, antimycin A, 2-deoxy-D-glucose, iodoacetate), alone or in combination, on effector cell efficiency and intracellular ATP level. The inhibition of both aerobic and anaerobic energy production in the effector cells completely abolished cytotoxicity. An inhibition of 50% was observed when the intracellular ATP concentration was decreased to levels corresponding to 30 to 50% of those in the untreated controls.
Induction of T Lymphocyte Responses to a Small Molecular Weight Antigen
Authors: Bullock Wesley W. , Katz David H. , Benacerraf Baruj
Published: December 2022

2,4-Dinitrophenyl (DNP) coupled to the copolymer D-glutamic acid and D-lysine (D-GL) induces B cell tolerance but not T cell tolerance. This implies either a lack of DNP determinant recognition by T cells or a substantial difference in tolerance mechanisms for the two cell types. In the present study D-GL was conjugated with the well-defined determinant azobenzenearsonate (ABA) coupled to single amino acids shown here and previously by others to trigger effectively T lymphocytes. The experiments presented here demonstrate that these ABA conjugates of D-GL, although capable of diminishing anti-ABA antibody production, completely fail to render ABA-specific T lymphocytes tolerant thus drawing us to conclude that there are significant operational differences in the mechanisms of tolerance induction in T and B lymphocytes, respectively.
The Expression of ϑ-Like Antigen by Rat Peripheral Lymphocytes: Serologic and Functional Studies
Authors: Douglas Tommy C. , Dowsett Andrew P.
Published: December 2022

AKR/Cum mice (Thy-1b = ϑC3H) immunized with nucleated cells from WF rat thymus, Peyer's patches, peritoneal exudate, mesenteric lymph nodes, blood, bone marrow, or spleen produced antibodies cytotoxic for AKR/J (Thy-1a = ϑAKR) but not for AKR/Cum thymocytes. The specificity of these antibodies for the Thy-1.1 (ϑ-AKR) antigen was confirmed by tests using thymocytes from backcross mice segregating at the Thy-1 locus. This result suggested that the rat lymphocyte antigen cross-reactive with Thy-1.1 was expressed by at least some members of each of the rat lymphoid cell populations tested. AKR/Cum mice immunized with killed rat cells also produced anti-Thy-1.1 antibodies; thus indicating that further differentiation of the injected cells was not a prerequisite for the anti-Thy-1.1 response.

Unexpectedly, about 9% of unimmunized adult AKR/Cum males were found to be producing antibodies against Thy-1.1. To our knowledge, natural antibodies of this specificity have not been previously reported.

Finally, it was found that peritoneal exudate cells taken from WF rats previously immunized with EL4 mouse leukemia cells were neither killed nor functionally inactivated by treatment with anti-Thy-1.1 antibodies and complement.
An Antigenic Determinant Unique to the Hinge of γ3 Heavy Chains
Authors: Franklin Edward C. , Frangione Blas , Adlersberg Jay B.
Published: December 2022

The heavy (H)2 chain (γ3) of the IgG3 subclass of human immunoglobulins has a molecular weight of 60,000, in contrast to the 50,000 value reported for the γ1, γ2 and γ4 H chains. The γ3 hinge (interdomain) region is unusual in containing approximately 100 amino acid residues of which almost half consist of proline and cysteine in a series of repetitive sequences (1). This repetition creates an extra fragment which accounts for the extended size of the γ3 H chain. The availability of a γ3 heavy chain disease (HCD) protein Omm-s, which lacked the VH and CH1 domains but appeared to contain virtually the entire hinge region, permitted the ready isolation of an extended hinge fragment.

Antisera prepared against this protein could be made specific for a determinant associated with this interdomain region by appropriate absorptions.
Effects of Intravenous Silica on Immune and Non-Immune Functions of the Murine Host
Authors: Levy Michael H. , Wheelock E. Frederick
Published: December 2022

Silica, an agent toxic for macrophages, administered i.v. to DBA/2 mice rapidly depresses the clearance of colloidal carbon by the reticuloendothelial system and reduces the in vitro phagocytic activity of peritoneal macrophages harvested 3 days after silica injection. Silica blocks the humoral immune response to sheep erythrocytes and the cell-mediated immune response to allogeneic fibroblasts when given before antigen. Silica also induces complex alterations in spleen cell responsiveness to concanavalin A involving both local and serum factors. Silica had no significant effect on the induction of interferon by statolon or Newcastle disease virus. No unequivocal evidence was obtained that silica has a direct depressive effect on cells other than macrophages, but indirect effects on lymphocytes were produced most likely by factors released from silica-lysed macrophages. Intravenous silica may prove useful for the separation of interferon induction and immune response stimulation in studies of host resistance to infection and oncogenesis. Considerable variation exists in the immunodepressive effects of different preparations of silica.
The Primary Structure of a Rat κ Bence Jones Protein: Phylogenetic Relationships of V- and C-Region Genes
Authors: Starace Vincenzo , Querinjean Pierre
Published: December 2022

The complete amino acid sequence of a LOU rat κ Bence Jones protein, S211, is presented. The availability of such a sequence makes it possible to re-evaluate the phylogenetic relationships of V- and C-region genes.

The data suggest that V- and C-genes, and also V-genes between themselves, have evolved at different rates.

The Vκ1-gene seems to have been preserved during evolution and its products could be identified in three other species. The differences between these Vκ1 like sequences and a human Vκ1 representative sequence are similar and fall inside the range of inter-subgroup differences. On the other hand, the comparison of Cκ-regions from four different species agrees with their recognized phylogenetic relationships.

Evidence is presented which suggests that two substitutions within the C-region of the S211 κ-chain are unrelated to allotypes and presumably represent somatic events or are evidence for multiple isotypes of rat Cκ-region.
The Expression on Mouse Lymphoid Cells of Th-B, an Antigen Common to Mouse B Cells and Thymus Cells
Authors: Yutoku Masamichi , Grossberg Allan L. , Pressman David
Published: December 2022

A new cell-surface antigen of mouse lymphocytes, which was found earlier on normal and malignant plasma cells and about half the normal thymus cell population, has been shown to be on mature B cells and on the least immunocompetent subpopulation of cells of the thymus. The antigen was first detected by the cytotoxic effect on relevant cells of an in vivo purified rabbit antiserum raised against cells of the mouse IgM-producing plasma cell tumor MOPC-104E. We have now used a cell-transfer method to examine the effect of this antiserum (RantiM104E) on immunocompetent lymphocytes of spleen, including separated splenic B and T cells and thymus and bone marrow cells. We have found the antigen on the immunocompetent B lymphocytes of the spleen, but not on any other of the immunocompetent cells examined. The method involves determining the effect of the antiserum on the development of plaque-forming cells in the spleens of irradiated mice that have received lymphocytes from immune or non-immune donors by treating the lymphocytes with RantiM104E antiserum before transfer. Plaque-forming cells are suppressed when antiserum-treated spleen cells are transferred to the irradiated mice. This suppression was found to be due to action on only the splenic B cells. The helper activity of splenic T cells was not reduced significantly by antiserum treatment. Neither was the helper activity of thymus cells similarly treated reduced by the antiserum. We found, in fact, that the subpopulation of the thymus cells which is resistant to the antiserum was more immunocompetent than the total thymus cell population. In addition, the hydrocortisone-resistant thymus cells were also found to be resistant to the cytotoxic action of the antiserum. The antiserum had no effect on bone marrow cells in the cell-transfer procedure. The antigen involved, which we are designating “Th-B” appears to be a B cell line marker which appears relatively early during the differentiation of mouse B cells from precursor cells and is lost during maturation of T cells.
Immunologic Activity of Myelin Basic Protein in Strain 2 and Strain 13 Guinea Pigs
Authors: Kies Marian W. , Driscoll Bernard F. , Lisak Robert P. , Alvord Ellsworth C.
Published: December 2022

The resistance of Strain 2 guinea pigs to experimental allergic encephalomyelitis (EAE) induced by inoculation with whole CNS tissue in complete Freund's adjuvant (CFA) has been confirmed. This resistance is even more pronounced when myelin basic protein (BP) is used in attempts to induce EAE. Strain 2 guinea pigs are also resistant to an immunization schedule (multiple injections with BP in IFA followed by a single injection of BP in CFA) known to induce significant levels of antibody in susceptible strains. The poor response of Strain 2 guinea pigs to BP is not the result of lack of specific B cells—antibody equivalent to that produced by Strain 13 animals is obtained when the inoculum contains 0.5 mg BP and 2.5 mg mycobacteria.
Activation of Alveolar Macrophages after Lower Respiratory Tract Infection
Authors: Johnson James D. , Hand W. Lee , King Neva L. , Hughes Carl G.
Published: December 2022

Alveolar macrophage function has been studied in relation to bacterial infection of the lower respiratory tract. First, LRT macrophages were examined after exposure of rabbits to Listeria monocytogenes aerosols. Macrophages obtained from the LRT of animals 10 to 48 days after infection were activated, as evidenced by greater adherence to culture dishes and increased ability to ingest and kill both the original infecting organism and unrelated organisms, when compared to normal alveolar macrophages. Next, the in vitro effects on normal alveolar macrophages of incubation supernatants of control and antigen-stimulated lymphocytes (LRT and lymph node) from animals infected with L. monocytogenes or Streptococcus pneumoniae were evaluated. As manifested by increased adherence and phagocytosis, and an enhanced nonspecific bactericidal activity, alveolar macrophages were activated by the antigen-stimulated supernatants. These stimulated lymphocyte supernatants contain lymphokines (MIF), but the exact nature of the alveolar macrophage activating factor(s) remains to be determined. These observations, together with recent evidence that alveolar macrophages respond to lymphokines (MIF), suggest that the effector mechanism for cell-mediated immunity in the LRT is intact.
Antagonism of B Lymphocyte Mitogenesis by Anti-Immunoglobulin Antibody
Authors: Schrader John W.
Published: December 2022

Anti-mouse-immunoglobulin-antibodies (AMIg) were shown to suppress mitogenesis in B lymphocytes that were cultured with lipopolysaccharide, (LPS), or polymerized-flagellin, (POL). Preincubation of spleen cells with AMIg plus LPS had a greater suppressive effect on a subsequent mitogenic response to LPS than did preincubation with AMIg alone. Preincubation with LPS alone had, if anything, a slight enhancing effect. These experiments suggested that AMIg did not suppress mitogenesis by interference with the initial binding of the mitogen, but rather exerted a separate negative effect that occurred subsequent to, or in the process of, B cell-stimulation.
Thymus Influence on the Conversion of 19S to 7S Antibody Formation in the Response to TNP-Brucella
Authors: Romano Thomas J. , Thorbecke G. Jeanette
Published: December 2022

Serially transferred LAF1 spleen cells show a deficient 7S PFC response to TNP-Brucella when Tx as compared to normal irradiated intermediate hosts are used. This defect can be corrected by combining the spleen cells with lymph node cells from the Tx intermediate hosts. It is concluded that T helper cells, residing primarily in lymph node, are needed for efficient 19S→7S conversion in the immune response.
Pretreatment of Murine Thymocytes by Phytohemagglutinin Inhibits the Binding of 3H-Concanavalin A
Authors: Ozato Keiko , Ebert James D. , Adler William H.
Published: December 2022

The binding of 3H-concanavalin A (Con A) to cortisone-resistant and normal mouse thymocytes, which greatly differ in mitogenic responsiveness, was compared. Almost equal numbers of 3H-Con A molecules (7 × 105 molecules per cell) were found to bind to both cell types, and the rates of 3H-Con A binding were nearly identical.

The binding capacity of thymocytes for 3H-Con A decreased rapidly after removal from the thymus and incubation in protein free synthetic medium. Similarly, mitogenic responsiveness dropped rapidly after cells were exposed to this medium. 3H-Con A molecules bound to cells were dissociated from them after a brief incubation, about 30% of radioactivity being lost in 2 hr with increasing radioactivity being found in the supernatant.

When cells were pretreated with PHA-P, which is a T cell mitogen, their mitogenic responsiveness to Con A was suppressed along with 3H-Con A binding to the cells. In contrast, a B cell mitogen, LPS, that has a synergistic effect on the Con A mitogenic response in thymocytes had no effect on binding of 3H-Con A to thymocytes.
A Method for Detection of Ia Antigens in the Absence of Appropriate H-2 Recombinants
Authors: Hauptfeld Miroslav , Hauptfeld Věra , Klein Jan
Published: December 2022

A method is described which obviates the use of H-2 recombinant strains for production and detection of Ia antibodies. The antibodies are produced by immunization with spleen cells in a strain combination in which the donor differs from the recipient either in the K end of the H-2 complex or in the whole complex. If the right schedule is used, this immunization produces antibodies against both H-2 and Ia antigens. The H-2 antibodies are absorbed out with erythrocytes or T lymphocytes rendering the antiserum specific for Ia antigens. The presence of Ia antibodies is asserted by determining the tissue distribution of the antigens detected with the absorbed antiserum. Another antiserum is then prepared in the same strain combination by immunization with tissue that does not contain Ia but does contain H-2 antigens (e.g., a sarcoma of the proper genotype). The second antiserum contains only H-2 antibodies and the presence of these antibodies is again asserted by determining the tissue distribution of the corresponding antigens. The molecular distinctiveness of the putative Ia and H-2 antigens is then demonstrated by the newly developed technique of antibody-mediated induction of resistance to cytotoxicity (lysis). If the antigens detected with the two antisera move independently in the cell membrane, and if the antigens detected with the first antiserum do indeed have Ia-like properties, it is concluded that the antiserum detects Ia antigens. This method should prove to be useful for detection of Ia antigens in H-2 haplotypes for which no intra-H-2 recombinants are known, and for detection of Ia-like antigens in other mammalian species, particularly in man.
Generation of Cytotoxic T Lymphocytes in Vitro
Authors: Engers Howard D. , Thomas Karl , Cerottini Jean-Charles , Brunner K. Theodor
Published: December 2022

Subcellular particulate membrane fragments prepared from murine lymphoid or tumor cells were used as a cell-free antigen source in order to stimulate the generation of cytolytic thymus-derived effector cells (CTL) in vitro. When cultivated with normal spleen cells as a source of responding lymphocytes, particulate antigen preparations induced only low CTL activities; in contrast, virtually normal responses were observed when immune spleens were used as a source of responding cells. In both cases, results were compared to those responses obtained with intact irradiated (1000 rads) normal spleen cells as stimulating antigen. The effector cells generated with particulate antigen preparations (obtained either by hypotonic shock or by sonication) were shown to be T cells and were characterized with regard to the kinetics of their response and their dose-activity relationship. It was also shown that the responses observed were specific, both at the level of initiation and at the effector level. The results obtained suggest that there exists a fundamental difference between normal and alloimmune spleen cells in their ability to respond in vitro to stimulation by subcellular antigen preparations.
Peyer's Patches, Gut IgA Plasma Cells and Thymic Function: Study in Nude Mice Bearing Thymic Grafts
Authors: Guy-Grand Delphine , Griscelli Claude , Vassalli Pierre
Published: December 2022

Nude mice have poorly developed Peyer's patches with very small or no germinal centers and little lymphoid cell proliferation, and a marked decrease in the number of gut-IgA plasma cells. Thymus grafts, which restore the T lymphocyte population of their lymphoid organs to nearly normal levels, lead to a considerable development of the Peyer's patches and of their germinal centers, associated with a considerable increase in gut IgA plasma cells, and in the serum IgA level. These findings are consistent with the postulated relationship between the Peyer's patches germinal center cells and the gut IgA plasma cells, and might help to explain the association of thymic defects, low serum IgA, and lack of intestinal IgA plasma cells observed in some immunodeficiency syndromes of man. Nude mice also have a marked decrease in the number of lymphocytes present within the intestinal epithelium. These intraepithelial lymphocytes, which have been shown to be of T nature, are restored to normal numbers after thymus grafting.
The Molecular Basis of Self-Association of IgG-Rheumatoid Factors
Authors: Pope Richard M. , Teller David C. , Mannik Mart
Published: December 2022

The intermediate complexes, sedimenting between 19S and 6.6S components of normal serum on analytical ultracentrifugation, were purified from plasma of three patients with rheumatoid arthritis. Sequential gel filtration and removal of contaminants by agarose-antibody immunoadsorbents were employed for purification of these complexes. The isolated complexes from the three patients consisted of IgG with κ and λ light chains.

Sedimentation equilibrium ultracentrifugation experiments showed that the isolated complexes underwent concentration-dependent self-association, whereby the smallest detectable molecular species had a molecular weight of 292,000. These IgG dimers were formed by self-association of IgG-rheumatoid factors, since nearly all F(ab′)2 fragments, prepared from the isolated complexes by pepsin digestion, bound to normal IgG. The association constants for the interaction between normal IgG and one binding site of the F(ab′)2 fragments were about 105 liters/mole. Since a cyclic structure with two antigen-antibody bonds was thought to form in the self-association of two IgG-rheumatoid factors, the association constant for dimer formation was calculated to be 1010 liters/mole. The preferential self-association of IgG-rheumatoid factor was supported by the observation that monomeric normal human IgG did not replace the IgG-rheumatoid factor when the complexes were dissociated and reformed in the pressence of excess normal IgG.

The self-association of IgG-rheumatoid factors may be a general phenomenon in rheumatoid arthritis, as suggested by the observations of other investigators.
The Induction and Abolition of Specific Immunosuppression of Heart Allografts in Rats by Use of Donor Blood and Cyclophosphamide
Authors: Marquet Richard , Heystek Gerard
Published: December 2022

Intravenous pretreatment of WAG/Rij rats with BN blood 14 days before transplantation leads to permanent survival of BN heart allografts. Pretreatment with donor blood in the reverse donor-host combination gives rise to accelerated rejection of WAG/Rij hearts. Addition of 100 mg/kg Cy or 50 mg/kg Cy to the pretreatment with donor blood in the WAG/Rij to BN model resulted in permanent graft acceptance, presumably due to the phenomenon of immunologic enhancement. This effect could be observed only if the interval between drug administration and antigen pretreatment was short. The use of Cy had a more profound and long-lasting effect on humoral than on cellular immunity. Addition of 100 mg/kg Cy to the active enhancement protocol in the “easy” BN to WAG/Rij combination produced permanent graft survival in an immunologic setting reminiscent of immunologic tolerance. The combined pretreatment with donor blood and 50 mg/kg Cy in this donor-host combination abolished the operation of immunologic enhancement, which could be induced if donor blood was given alone.
Activation by Some T-Independent Antigens and B Cell Mitogens of the Alternative Pathway of the Complement System
Authors: Bitter-Suermann Dieter , Hadding Ulrich , Schorlemmer Hans-Ulrich , Limbert Michael , Dierich Manfred , Dukor Peter
Published: December 2022

A number of T-independent antigens and B cell mitogens were examined for their ability to activate C3 via the alternative pathway of the complement system. Loss of hemolytically active C3, generation of anaphylatoxin activity, and immunoelectrophoretic conversion of C3 and factor B, were checked in normal and C4-deficient guinea pig serum, and, in some cases, in normal human serum. As judged by their activity in these assays, 10 lipopolysaccharides of different origin and constitution, pneumococcus type III polysaccharide, levan, dinitrophenylated aminoethyl-dextran, dinitrophenylated (D-glutamic acid, D-lysin) copolymer, polymerized flagellin, and pokeweed mitogen were all capable of initiating the alternative pathway, but differed with respect to their potency, their relative activity in the presence or absence of C4, and their ability to inhibit C3-turnover at high concentrations. Polyvinylpyrrolidone of intermediate molecular weight (4 × 104 daltons) was only active if the most sensitive assay was used (anaphylatoxin generation). Other species of polyvinylpyrrolidone, depolymerized pneumococcal polysaccharide, aminoethyl-dextran, [D-glutamic acid, D-lysin] copolymer, phytohemagglutinin and concanavalin A failed to activate C3. C3-consumption by concanavalin A was due to nonspecific binding.
Genetic Control of Susceptibility to Experimental Allergic Encephalomyelitis and the Ag-B Locus of Rats
Authors: Gasser David L. , Palm Joy , Gonatas Nicholas K.
Published: December 2022

Injection of guinea pig spinal cord with complete Freund's adjuvant induces EAE in Lewis (Ag-B1) and DA (Ag-B4) rats, but not in rats of the BN (Ag-B3) strain. When BN is crossed with Lewis, susceptibility is determined by a gene linked to the Ag-B histocompatibility locus, but a much more complex mode of inheritance is involved when BN and DA rats are crossed. Six inbred strains possessing the Ag-B1 histocompatibility allele have been found to be susceptible to EAE. Evidence for recombination between the Ag-B locus and the gene determining susceptibility to EAE has not yet been obtained.
Regulation of Lymphocyte Trapping: The Negative Trap
Authors: Zatz Marion M. , Gershon Richard K.
Published: December 2022

Suppression of 51Cr-labeled lymphocyte homing to the spleen occurs after administration of insoluble protein antigen and as a late sequela to the graft-vs-host response (GVHr). This decrease in splenic localization of labeled cells, termed “negative trapping,” has elements of immunologic specificity in that tolerance induction or presensitization abrogates the negative trap. Increasing the dose of antigen accelerates the appearance of the negative trap, which is, however, evanescent, lasting from 24 to 48 hr.

Synergistic and antergistic regulation of the GVHr-induced lymphocyte trap is produced by populations of 850 R-irradiated thymocytes and by F1 cortisone-resistant thymocytes. The time at which these subpopulations cause suppression or amplification of the lymphocyte trap correlates with the activity of the GVHr-producing inoculum.

These findings suggest that regulation of lymphocyte traffic may provide a mechanism for control of immune responses in vivo.
The Enhancing Effect of Mitogens on the in Vivo Immune Response of Rabbits
Authors: Romball Carole G. , Weigle William O.
Published: December 2022

The effect of Con A and PHA on the primary humoral immune response in rabbits was investigated and compared with the effect of LPS and irradiation. Both Con A and PHA enhanced PFC levels and precipitating antibody titers to HuIgG when injected simultaneously with AHuIgG. Comparable enhancement of the response to HuIgG was obtained by simultaneous injection of LPS with AHuIgG or by irradiating rabbits (500 R) 24 hr after injection of the antigen. Further studies with Con A showed that its adjuvant effect was not restricted to a particular antigen since it also enhanced antibody responses to both SRBC and Bov Tg when injected simultaneously with either of these antigens. Although optimal enhancement of the response to HuIgG occurred when antigen and mitogen were injected simultaneously, some enhancement was obtained if Con A was injected 2 days after antigen, whereas the response was decreased if Con A was injected 2 days after antigen, whereas the response was decreased if Con A was injected 2 days before antigen. Splenic PFC in A/J mice injected with doses of AHuIgG and Con A equivalent on a body weight basis to those used in rabbits were also enhanced by simultaneous injection of Con A with the antigen.
Distribution of Covalently Bound and Non-Covalently Bound Secretory Component on Subclasses of Rabbit Secretory IgA
Authors: Knight Katherine L. , Vetter Marsha L. , Malek Thomas R.
Published: December 2022

The distribution of non-covalently bound secretory component (SC) on the two subclasses, IgA-f and IgA-g of rabbit secretory IgA (sIgA) was determined; the two subclasses were separated from each other by the use of antibody-immunosorbent columns and were subjected to SDS polyacrylamide gel electrophoresis. No SC appeared to be dissociated from the IgA-f molecules from each of 11 different rabbits; the IgA-g molecules, however, did have SC which was dissociated by SDS. Thus, all of the non-covalently bound SC on rabbit sIgA resides on the IgA-g subclass molecules.
The Protein Nature of the Thy-1.2 Alloantigen as Expressed by the Murine Lymphoblastoid Line S-49.1 TB·2·3
Authors: Kucich Umberto N. , Bennett J. Claude , Johnson Brian J.
Published: December 2022

This preliminary study was undertaken to investigate the chemical nature of the Thy-1.2 antigen expressed on the murine cell line S-49.1 TB·2·3 (S-49). The presence of the Thy-1.2 antigen was indicated by the inhibition of AKR anti-C3-Thy-1.2 serum induced lysis of 51Cr-primed target cells. It was found that limited digestion of S-49 cells with crude papain yielded a Thy-1.2-containing solution. The protein nature of the Thy-1.2 antigen obtained in this manner was indicated by changes after proteolytic digestion. Separate digestions with crystalline papain, insolubilized papain, and insolubilized protease all destroyed the Thy-1.2 activity. These results suggest that the protein moiety is necessary for Thy-1.2 activity.
Immunochemistry of Hepatitis B Surface Antigen (HBsAg): Preparation and Characterization of Antibodies to the Constituent Polypeptides
Authors: Shih J. Wai-Kuo , Gerin John L.
Published: December 2022

The structural polypeptides of HBsAg were shown to be immunogenic in guinea pigs. Purified 22-nm forms of the ad and ay subtypes of HBsAg were solubilized under reducing conditions and electrophoresed in SDS-polyacrylamide gels. Individual polypeptides isolated from both HBsAg/ad and HBsAg/ay subtypes were used to hyperimmunize guinea pigs using Freund's complete adjuvant. All antimals produced specific antibodies against native HBsAg as determined by complement fixation, passive hemagglutination, and double-antibody radioimmunoprecipitation assays. Each polypeptide contained within its structure the group-specific HBsAg determinant, a. Equilibrium competitive inhibition studies were conducted to determine the relative affinities of antisera produced against the major HBsAg polypeptides P-1, P-2, and P-6 (23,000, 29,000, and 72,000 daltons, respectively.)
Antigenic Competition Between Two Sequentially Acting Antigens
Authors: Monier J. C.
Published: December 2022

This study concerns the antigenic competition among heterologous red cells, a T suppressor-dependent phenomenon, in three cases, when the two antigens are administered by various routes, in (a) splenectomized mice or in Nude mice reconstituted with (b) lymph node cells, or spleen cells.

Competition occurs whatever the routes of antigenic introduction, except when the two antigens are injected subcutaneously in the same leg and the anti-SRC plaque-forming cells are counted in the draining lymph nodes. In that case, the first antigen plays the role of adjuvant to the second.

An adjuvant effect is also observed in splenectomized mice when the antigens are introduced intraperitoneally. However, competition does not occur in Nude mice but is present when those animals have been reconstituted either with lymphnode cells or with spleen cells.

Those results play in favor of the presence of T suppressors, both in lymph nodes and in spleen; however, in lymph nodes, the immunosuppressive action induced by the first antigen is exceeded by a concomitant adjuvant effect.
Expression of Mouse Mammary Tumor Viral Polypeptides in Milks and Tissues
Authors: Noon Marian C. , Wolford Ronald G. , Parks Wade P.
Published: December 2022

A 14,000-dalton polypeptide (p14) from RIII murine mammary tumor virus (MMTV) has been isolated by column chromatography in 6 M GuHCl. Antiserum prepared in rabbits specifically precipitated 125I-labeled p14; in double antibody competition, radioimmunoassays performed with limiting amounts of antibody, both purified p14 and disrupted MMTV, competed specifically with labeled antigen. The expression of this MMTV type B virus antigen could be measured by competition radioimmunoassays in milks, mammary glands, tumors, and tissue culture cells. MMTV expression measured by p14 immunoassay correlated well with the spontaneous incidence of mammary adenocarcinomas in different murine strains but not with type C MuLV p30 antigen expression. Levels of MMTV gp52, the major type-B viral glycoprotein, corresponded to p14 levels, suggesting that their control is comparably regulated. Evidence that this low m.w. polypeptide is present in feral and inbred strains of widely differing geographic origin and in MMTV with apparently different biologic properties suggests surprising conservation of MMTV protein homology.
Analysis of Sera from SV40-Immunized and Tumor-Bearing Hosts for Blocking Activity and Antibody-Dependent Cellular Cytotoxicity
Authors: Lausch Robert N. , Sofranko John , Prather Suzanne O.
Published: December 2022

The role of serum factors in tumor immunity to cells transformed by PARA-(defective SV40)-adenovirus 7 was investigated. It was found that sera from SV40-sensitized hosts did not block the specific cytotoxicity of SV40-sensitized spleen cells for PARA-7 cells. However, such sera could collaborate with nonsensitized spleen cells to produce specific killing. This activity could be absorbed out by PARA-7 cells but not by cells transformed by cytomegalovirus.

The activity of sera from hamsters bearing tumor isografts depended upon when, after transplantation, the specimens were obtained. Sera collected ≧ 10 days after grafting completely blocked immune spleen cell cytotoxicity and did not mediate target cell killing in the presence of normal spleen cells. Sera obtained at an earlier time, i.e., 3 to 6 days after transplantation, consistently were active in the antibody-dependent cellular cytotoxicity test and exhibited reduced or no blocking of antibody-independent cellular cytotoxicity. Thus, there appears to be an inverse correlation in the capacity of serum from tumor bearing hosts to block effector cell cytotoxicity and mediate antibody-dependent cellular cytotoxicity.
Immunogenetic Analysis of H-2 Mutations
Authors: Forman James , Klein Jan
Published: December 2022

The H-2da haplotype was derived from the H-2d haplotype by a mutation localized to the D end of the H-2 complex. Coculture of H-2d and H-2da spleen cells gives rise to bidirectional MLR. However, the H-2d anti-H-2da response is much stronger than that of H-2da anti-H-2d. Both haplotypes gives rise to reciprocal CML. B10.D2(R103) strain spleen cells, which differ only at the D end of the H-2 complex from the H-2d haplotype, kill H-2da target cells in CML when sensitized to H-2d stimulators and vice versa. Therefore, both the mutant and strain of origin share a D end CML specificity. H-2d and H-2da reject skin grafts in both directions, although some H-2d grafts show prolonged acceptance on H-2da recipients. These data are consistent with a mutation in the D end of the H-2d haplotype resulting in gain-loss of an antigen(s) that gives rise to reciprocal MLR, CML, and skin graft rejection. Further, the mutant can be distinguished from the strain of origin on the basis of the strength of immune response in MLR.
The Identification of HL-A Antigens on Fresh and Cultured Human Endothelial Cells
Authors: Gibofsky Allan , Jaffe Eric A. , Fotino Marilena , Becker Carl G.
Published: December 2022

Human endothelial cells were obtained from the umbilical cord veins of 16 newborns by methods previously described and tested for HL-A antigens by a microcytotoxicity method. HL-A antigens were present on all endothelial cell lines tested. When the HL-A phenotypes of fresh endothelial cells and autologous fetal lymphocytes were compared, a concordance of 70% was observed. When the HL-A phenotypes of maternal lymphocytes and fresh endothelial cells were compared, a maternal contribution to the endothelial cell phenotype was evident in 72% of the possible common antigens. Some HL-A antigens were deleted from 11 of 16 endothelial cell lines that were re-typed after 2 weeks in tissue culture. The majority (90%) of deleted antigens were from the second HL-A locus. When three lines of endothelials cells were again re-typed after 6 weeks in culture, no further changes in antigenicity were noted. These findings: a) demonstrate that HL-A antigens are present on human endothelium and suggest that endothelial cells are actively involved in establishing the immunogenicity of a graft, and b) demonstrate that the HL-A antigens on human endothelial cells may be modulated by in vitro culture.
Class, Amounts and Affinities of Anti-Dinitrophenyl Antibodies in Chickens
Authors: Yamaga Karen , Benedict Albert A.
Published: December 2022

Repeated intravenous injections of maximally coupled dinitrophenylated bovine γ-globulin elicited both 7S and 17S anti-dinitrophenyl antibodies in chickens. Only antibodies of low affinity were produced regardless of the priming dose, the interval between injections, and the number of injections. The 7S and 17S antibodies isolated from individual animals had identical affinities and heterogeneity indices. The concentrations of antibodies formed were uniformly low despite many injections over a prolonged period. These studies indicate that stimulation by antigen alone may not be sufficient for the induction of predominant 7S antibody formation and for the synthesis of high affinity antibody.
Class, Amounts, and Affinities of Anti-Dinitrophenyl Antibodies in Chickens
Authors: Yamaga Karen , Benedict Albert A.
Published: December 2022

The response of chickens given a single intramuscular injection of maximally coupled dinitrophenylated-γ-bovine β-globulin in either Freund's complete (FCA) or incomplete (FIA) adjuvants was characterized by an initial synthesis of 7S and 17S antibodies followed by the exclusive and persistent production of 7S antibodies. The 17S antibodies were not detected either 3 to 4 weeks after a single injection or after an intravenous boost 16 months later. Injections of low doses of antigen in FCA induced the synthesis of 7S antibodies of high affinity at least by 4 months. Analyses of the Sips plots generated from equilibrium dialysis data indicated that a shift in the distribution of 7S antibody affinities occurred because of the production of a restricted population of high affinity antibodies. The changes in the binding properties of antibody during the immune response from chickens given antigen in FIA were less apparent, although qualitatively similar, to those found in birds given antigen in FCA. Three possibilities were presented to explain the effect of adjuvant on the class and affinity of the antibody: a) the requirement of a second signal for B cell differentiation, b) the presence of subpopulations of B cells, and c) somatic mutation events.