bluuebunny/crossref_metadata_2025 huggingface dataset:
REGULATION OF IMMUNOGLOBULIN SYNTHESIS BY DEXTRAN
Authors: Battisto Jack R. , Pappas Frances
Published: June 2004

Dextran, of the variety commonly used as plasma expander, markedly altered antibody synthesis to an unrelated antigenic stimulus, SRBC, in two animal species, guinea pig and mouse. The time at which dextran was administered relative to antigen was found to be most critical for increasing or decreasing the number of IgM and IgG PFC. Furthermore, these times differed for the two species studied.

Typically, when given to guinea pigs 6 h before SRBC, dextran caused a 20-fold rise in IgM-producing cells but had little effect upon IgG synthesis. However, if dextran preceded antigen by 24 h the same magnitude of increase was seen in IgG-forming cells while a decrease in IgM-producing cells occurred.

In mice, a short 2 h interval between dextran and antigen favored cells synthesizing IgG and not those producing IgM. A longer 6 to 24 h lapse between dextran and antigen resulted again in an inverted pattern, i.e., an increase in IgM and a decrease in IgG-producing cells.

In both species, if dextran was given 48 h before antigen, synthesis of IgG markedly decreased.

At the cellular level dextran activated those B cells already in the vascular compartment. In stimulating the IgM response to SRBC, dextran appears either to substitute for T cells or to amplify the effects of that small number of T cells still present in bone marrow preparations. Dextran-altered mouse B cells synthesized SRBC-specific IgG in the presence of normal T cells at an earlier time than did normal B and T cells. However, dextran was unable to cause blastogenesis in vitro of guinea pig lymph node cells or mouse B, T, and spleen cells.

The data suggest at least two effects that T cells exert upon B cells. One is to stimulate more B cells to produce IgM, a function accomplished by endotoxins, PWM, PPD, and the simple polysaccharide dextran. The other is to trigger shifts in synthesis of immunoglobulins M and G. Our observations are compatible with the view that a single cell is capable of synthesizing both of these immunoglobulins and that the stimulating factor for one may cause cessation of the other.
PRODUCTION OF A RUNTING SYNDROME AND SELECTIVE γA DEFICIENCY IN MICE BY THE ADMINISTRATION OF ANTI-HEAVY CHAIN ANTISERA
Authors: Murgita Robert A. , Mattioli Carlos A. , Tomasi Thomas B.
Published: June 2004

Conventional Swiss mice were treated from birth with intraperitoneal injections of anti-immunoglobulins in an attempt to create an experimental dysgammaglobulinemia. Mice treated with anti-γM were immunologically suppressed in all immunoglobulin classes as determined by serum antibody titers, splenic plaque-forming cells, serum immunoglobulin levels, and immunofluorescent analysis of plasma cells in lymphoid tissues. Treatment immediately after birth with high concentrations of anti-γM leads to a developmental arrest characterized by severe immunosuppression, failure to gain weight, and premature death. The pathogenesis of anti-γM runting syndrome is unknown. Animals similarly treated with anti-γG, anti-γA, or control normal goat or rabbit γ-globulins developed normally. The frequency of occurrence and severity of anti-γM-induced runting syndrome is dependent upon the concentration of anti-γM-globulin administered.

Administration of anti-γA resulted in a selective γA deficiency that was characterized by a marked reduction in serum-γA and an absence of γA-containing cells in the spleen. However, essentially normal numbers of plasma cells were found in the gastrointestinal lamina propria of anti-γA-treated animals concomitantly with suppressed levels of γA in intestinal fluids.
SURFACE ANTIGENS OF MAMMALIAN CELLS AS GENETIC MARKERS. II
Authors: Wuthier Paul , Jones Carol , Puck Theodore T.
Published: June 2004

A second surface antigen, BL, lethal in the presence of specific antibody and complement has been identified on some human cells and shown to behave as a good genetic marker. It is autosomal, unlinked to the human AL antigen previously described, and unlinked to 15 other human genes. The AL antigen, which is linked to the lactic dehydrogenase A gene, is found on the HeLa, the cultured human fibroblast, and in small amounts on the human lymphocyte. BL occurs on HeLa cells, on cultured human fibroblasts, and on human lymphocytes, but not on human RBCs. Hybrid cells formed by fusion of human and Chinese hamster cells have been prepared containing each of the four possible combinations of these two markers. Highly selective antisera sensitive to each marker separately can be obtained. The use of single-cell plating to demonstrate the presence of the antigens and of hybrid cells containing desired combinations of the markers facilitates study in this system.
PEROXIDASE-MEDIATED MAMMALIAN CELL CYTOTOXICITY
Authors: Edelson Paul J. , Cohn Zanvil A.
Published: June 2004

Lactoperoxidase, in the presence of hydrogen peroxide and iodide is cytotoxic for human and mouse lymphoid cells, and human erythrocytes. Myeloperoxidase, in amounts equivalent to 1.5 x 106 neutrophils, readily replaces lactoperoxidase, and allows the substitution of the iodide ion by chloride. The myeloperoxidase-mediated reaction is rapid, and highly efficient, leading to 85–90% cell death in 90 min, as measured by 51chromium release and dye exclusion. The mixture of granulocytes. monocytes, and lymphocytes present in an inflammatory exudate, and the intimate cell-to-cell association characteristic of cytotoxic phenomena may provide the in vivo requirements for such a system.
DIVERSE EXPRESSION OF GROUP a ALLOTYPE SPECIFICITIES ON THE HEAVY CHAINS OF HOMOGENEOUS RABBIT ANTIBODIES
Authors: Kindt Thomas J. , Seide Rochelle K. , Tack Brian F. , Todd Charles W.
Published: June 2004

Variations in the ability of homogeneous antibodies to absorb group a allotype antisera suggest that these VH region allotypes comprise a spectrum of specificities. While no homogeneous antibody tested would completely absorb antisera to the group a specificities, the total IgG preparations from individual rabbits was capable of doing so, including preimmune IgG from the rabbits that produced the homogeneous antibodies.

Differences in the serologic reactivities of homogeneous antibodies indicate that each possesses only a portion of the spectrum of the allotypic specificities expressed by the total IgG.
CELLULAR MEDIATORS OF ANTI-LISTERIA IMMUNITY AS AN ENLARGED POPULATION OF SHORT-LIVED, REPLICATING T CELLS
Authors: North Robert J.
Published: June 2004

An intravenous immunizing infection with the facultative, intracellular parasite, Listeria monocytogenes results in the production in the spleen of a population of immunologically-committed lymphocytes which can adoptively immunize normal recipients against a lethal challenge infection. These cellular mediators of immunity are first produced in the spleen between days 2 and 4 of infection and reach peak production on day 6. Their production then progressively decreases until about day 20 when their presence can no longer be detected.

Increased production of cellular mediators is coincident with major increases in cell division, cellularity, and spleen weight. Decreased production of cellular mediators, on the other hand, is associated with decreases in cell division, cellularity, and spleen weight. Again, the level of delayed sensitivity to Listeria antigens expressed by the host at any one time is proportional to the number of cellular mediators in the spleen.

Increased production of cellular mediators is also associated with major increases in the total numbers of replicating T cells and B cells in the spleen. That the cellular mediators of immunity are part of the replicating T cell population, rather than the B cell population, is evidenced by their susceptibility to anti-θ serum and by their resistance to anti-Ig serum. Furthermore, they can be completely eliminated from the spleen by a brief pulse of the antimitotic drug, vinblastine. This study allows the conclusion that the cellular mediators of anti-Listeria immunity belong to an expanded population of rapidly dividing, short-lived T cells. It is suggested that they have the same properties as the T cell effectors of allograft immunity.
MUTANTS OF NONPRODUCER CELL LINES TRANSFORMED BY MURINE SARCOMA VIRUSES
Authors: Hatanaka M. , Klein R. , Toni R. , Walker J. , Gilden R.
Published: June 2004

A variety of cell mutants were obtained by a single 5'-bromodeoxyuridine (BrdU) treatment of an nonproducer (NP) cell line transformed by the Kirsten strain of murine sarcoma virus (Ki-MSV). Isolation procedures of these cell

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mutants are described. The cell mutants obtained were classified by tumorigenic potential and shedding of Type C virus particles. The cell mutants were classified into four groups: (A) tumorigenic, without particles; (B) tumorigenic, with Type C particles; (C) nontumorigenic, without particles; and (D) nontumorigenic, with Type C particles. The tumorigenic cell lines showed variability in morphology with both flat and typical transformed appearing cell lines showing equal transplantability.
IMMUNOLOGIC STUDIES OF THE MAJOR NONIMMUNOGLOBULIN PROTEIN OF AMYLOID
Authors: Levin Mark , Pras Mordechai , Franklin Edward C.
Published: June 2004

Antisera have been prepared against the major nonimmunoglobulin component of secondary and familial Mediterranean fever (FMF) associated amyloid which has been called A component or acid soluble fraction (ASF). The antisera were shown to be monospecific for ASF by precipitation of 125I-labeled antigen and gave a reaction of identity with four different ASF preparations. The antisera were able to detect a circulating component in human serum that migrated in the α1-globulin region. This circulating component gave a line of identity with degraded ASF by double immunodiffusion. 57 normal sera and 89 sera from patients with diseases known to be frequently associated with amyloidosis were tested by immunodiffusion for the circulating ASF component. 7% of normal sera and 50–80% of the pathologic sera had elevated amounts of this component. Absorption studies showed that all normal sera probably have small amounts of this component while cord sera do not have detectable amounts. This component was partially purified and was shown to be slightly larger than albumin. The relation of the circulating component to the acid soluble fraction of amyloid is discussed.
SURFACE IgE ON HUMAN BASOPHILS DURING HISTAMINE RELEASE
Authors: Becker Karl E. , Ishizaka T. , Metzger H. , Ishizaka K. , Grimley Philip M.
Published: June 2004

The distribution of surface IgE on human basophils was studied using fluorescence microscopy and immunoferritin electronmicroscopy. Redistribution of the IgE was dose, time and temperature dependent and required divalent anti-IgE. Cells which can release histamine in vitro were indistinguishable in these respects from cells which cannot. The redistribution was unaffected by the presence or absence of Ca++.

No correlation between the conditions required for optimal histamine release and for redistribution was observed. At low doses, optimal histamine release occurred in the absence of, or before, redistribution. At higher doses redistribution occurred in the absence of histamine release. Antigen-induced histamine release was unaccompanied by gross redistribution of the surface IgE.

Since both histamine release and redistribution require bridging of IgE on basophils it is concluded that only certain kinds of cross-linking of the IgE effectively stimulates these cells.
PHYLOGENETICALLY ASSOCIATED RESIDUES WITHIN THE VHIII SUBGROUP OF SEVERAL MAMMALIAN SPECIES
Authors: Capra J. Donald , Wasserman Richard L. , Kehoe J. Michael
Published: June 2004

Immunoglobulin heavy chains from IgG pools of several mammalian species have been subjected to Edman degradation on an automated protein sequencer. The percentage of unblocked vs. blocked heavy chains was estimated from the yield of the invariant valine in the second position. Further analysis of these unblocked polypeptides unequivocally placed them in the VHIII subgroup on the basis of homology with known human heavy chain sequences.

The mammals studied could be divided into three distinct categories on the basis of the distribution of the VHIII subgroup. In several species the VHIII subgroup could not be detected while, in others, virtually all of the heavy chains belonged to this subgroup. Several species had intermediate amounts with the level of the VHIII subgroup restricted to between 19 and 29% of the total pool. Within experimental error, all members of a given order had a similar VHIII subgroup distribution.

Further amino acid sequence studies illustrated a high degree of structural homogeneity in the heavy chains of IgG isolated from pooled sera of a number of mammalian species. The very close amino acid sequence homologies of the amino terminal 24 residues of the various pools corroborated conclusions previously obtained using several myeloma proteins from some of these same species. In particular, certain phylogenetically associated residues were identifiable at characteristic positions in the pools in confirmation of their identification in the myeloma proteins. The simplest assumptions would suggest that these findings are more compatible with a pauci-gene than a multi-gene basis for the generation of antibody diversity.
STUDIES ON HUMAN PLASMA α2-MACROGLOBULIN-ENZYME INTERACTIONS
Authors: Harpel Peter C.
Published: June 2004

Human plasma α2-macroglobulin is an inhibitor of circulating proteases that function in hemostatic and inflammatory reactions but the biochemical nature of its interaction with these enzymes is not well defined. This investigation has found that α2-macroglobulin is comprised of subunit chains of 185,000 molecular weight as analyzed by electrophoresis in polyacrylamide gels containing sodium dodecyl sulfate. Trypsin, thrombin, plasmin, and plasma kallikrein in amounts completely bound to α2-macroglobulin attacked one region in the subunit chain producing a single derivative with a molecular weight of 85,000 indicating that hydrolysis occurred at or near the center of the parent chain. The proteolytic derivative was also identified in an α2-macroglobulin preparation from plasma incubated with the plasminogen activator, urokinase. α2-macroglobulin functionally capable of binding enzyme appeared to be required both for limiting tryptic hydrolysis and for confining the concentration dependent increase in the derivative chain to the 1st min of incubation since acid-denatured α2-macroglobulin that failed to bind trypsin was extensively degraded. Three derivative chains resulted from the interaction of α2-macroglobulin with chymotrypsin demonstrating the presence of at least two chymotrypsin susceptible regions in the precursor chain. Reduction of the α2-macroglobulin-enzyme mixture was required for the identification of the derivative subunit chains establishing that these cleavage products were covalently linked to the parent molecule by disulfide bridges. Thus, α2-inacroglobulin acts as a substrate for circulating proteases, a finding which may also pertain to the mechanism of action of other plasma enzyme inhibitors.
IDENTIFICATION OF HUMAN B AND T LYMPHOCYTES BY SCANNING ELECTRON MICROSCOPY
Authors: Polliack A. , Lampen N. , Clarkson B. D. , de Harven E. , Bentwich Z. , Siegal F. P. , Kunkel H. G.
Published: June 2004

In this study a variety of human lymphocytes of known B or T cell type, obtained from multiple sources, were prepared for scanning electron microscopy (SEM) by the critical point drying method. Distinction between normal B and T lymphocytes was relatively easy in most instances, on the basis of their surface architecture. Using immunological methods, between 20 and 30% of normal peripheral blood lymphocytes (PBL) were identified as B cells and from 69 to 82% as T cells. SEM results showed that 20% of the PBL had a complex villous surface and approximately 80% of cells were smaller and had a relatively smooth surface. Comparison of the above data and enrichment of B cells from PBL, by centrifugation after T cell rosettes had formed, indicated that the "villous" cells were B lymphocytes and the "relatively smooth" cells were T lymphocytes. T cells obtained from two human thymuses were also of the generally smooth cell type.

Further evidence for the distinction of B and T lymphocytes, on the basis of surface morphology, was obtained from the examination of cultured lymphoid cell lines of known B or T cell derivation. Cells from cases of chronic lymphocytic leukemia also provided support for the above interpretations. Five of six untreated cases were clearly of B cell type by immunologic and SEM criteria. One unusual case showed the presence of T and B lymphocytes in almost equal numbers by SEM and a mixture of B and T cells by immunologic markers. An additional case that had received chemotherapy showed numerous atypical cells that were difficult to classify by SEM.

Detailed examination of the smoother T cells showed that at least half of them had a moderate number of surface digitations and a small proportion had an intermediate surface morphology with a relatively large number of surface digitations. The latter presented difficulties in classification and may correspond to different stages of differentiation and represent subpopulations of lymphocytes.

The distinction between human B and T lymphocytes on the basis of their surface architecture can be made by SEM of critical point dried samples, with relative ease in most but not all instances. The effects of stimulation, cell cycle, differentiation, intercellular contact, and density of cell population, on the surface architecture of lymphoid cells, remain to be determined.
SELECTIVE DNA SYNTHESIS BY CELLS SPECIFICALLY LOCALIZING IN RESPONSE TO XENOGENEIC ERYTHROCYTES
Authors: Thursh Donald R. , Emeson Eugene E.
Published: June 2004

The present studies have shown that cells capable of specific localization in response to challenge with CRBC or SRBC synthesize DNA very rapidly during the period from 2–5 days (peak 3 days) post primary immunization. This has been done by incubating the antigenically stimulated lymphoid cells with [3H] or [14C]thymidine in vitro for 45 min before adoptive transfer to syngeneic recipients. Specifically localizing cells (SLC) labeled in this way may ultimately account for up to 50% of the 3H or 14C present in a set of specifically challenged lymph nodes 3 days later. The data presented are consistent with the hypothesis that SLC numerically constitute only a very small fraction of the total number of recirculating lymphocytes trapped in antigenically stimulated lymph nodes, and that the demonstration of specific localization therefore depends upon selectively labeling these SLC relative to other recirculating cells. Attempts to selectively label the RNA of SLC with the precursor uridine have to date met with only very limited success.
ACTIVATION OF THE ALTERNATE COMPLEMENT PATHWAY BY AUTOLOGOUS RED CELL STROMA
Authors: Poskitt Thomas R. , Fortwengler H. Philip , Lunskis Beverly J.
Published: June 2004

The present study demonstrates the ability of human autologous RBC stroma to activate the alternate complement pathway (C3-Activator system, properdin system), as evidenced by the generation of C3-Activator (C3A) from C3-Proactivator (C3PA) when RBC ghosts and sonicated ghosts are incubated with autologous serum. Intact RBC's, hemoglobin, and concentrated platelet stroma, on the other hand, are inactive in this regard. We postulate that this in vitro activity of RBC stroma may occur intravascularly when erythrocytes are damaged by immune or nonimmune mechanisms. The ensuing interaction of activated complement components with platelets leading to release of platelet factor three (PF-3) may constitute a mechanism for activation of the coagulation system during acute hemolytic episodes.
LATENT HERPES SIMPLEX VIRUS IN THE CENTRAL NERVOUS SYSTEM OF RABBITS AND MICE
Authors: Knotts F. B. , Cook M. L. , Stevens J. G.
Published: June 2004

Herpes simplex virus (HSV) type 1 induces a long-standing latent infection in the central nervous system of mice and rabbits. The infection was extablished in the brain stems of rabbits after corneal inoculation of the virus, and in the spinal cords of mice after rear footpad infection. In these animals, infectious virus could not be recovered by direct isolation from tissues; it was detected only after the tissues were maintained as organ cultures in vitro.
SEROLOGIC EVIDENCE FOR ANTIGENS CONTROLLED BY THE Ir REGION IN MICE
Authors: Götze D. , Reisfeld R. A. , Klein J.
Published: June 2004

Antibodies produced in B10.D2 mice against soluble lymphocyte membrane antigens of B10.A (H-2a) mice reacted only with lymphocytes of the strains carrying the Irk region, i.e., B10.A(2R), B10.K, B10.BR, B10.HTT, AQR, A.TE, C3H, and CBA; they did not react with cells of strains carrying different Ir regions, i.e., B10.A(4R), B10, B10.M, A.SW, DBA/1. It is therefore concluded that the antigen detected with these antibodies is apparently controlled by the Ir region of the H-2 complex. The antigen is present on some T lymphocytes and absent on B lymphocytes. Its presence or absence seems to correlate with MLC and GVH reactivity.
THE PRODUCTION OF MIGRATION INHIBITION FACTOR BY B AND T CELLS OF THE GUINEA PIG
Authors: Yoshida Takeshi , Sonozaki Hidekichi , Cohen Stanley
Published: June 2004

Stimulation of sensitized lymphocytes by specific antigen in vitro leads to the production of migration inhibition factor (MIF). In the case of the pure soluble protein, or hapten-protein antigens used in the present studies, this MIF production was a property of the T lymphocytes in the cell suspensions. When PPD was used, B cells, as well as T cells, produced MIF. Similarly, PPD could stimulate B cells to mediate the macrophage disappearance reaction, a reaction which is known to be a T cell-dependent in vivo manifestation of cell-mediated immunity. Suspensions of lymphocytes from nonimmune donors could also be stimulated by PPD; in this case, B cells, but not T cells, produced MIF. The factors produced by the two lymphocyte subpopulations appeared to be similar, if not identical, on the basis of physico-chemical criteria. It is suggested that PPD stimulates B cells for MIF production because of its role as a B cell mitogen. The ability of endotoxin lipopolysaccharide, another B cell mitogen, to also induce MIF production by B cells supports this contention. Thus, although activation of lymphocytes for MIF production by specific antigen is a property of T cells, B cells as well as T cells may be so activated by agents which act nonspecifically. This may prove to have implications for in vivo events involved in immunization. In addition, these observations lend further support to the concept that lymphokine production represents a general biologic phenomenon in addition to playing a role in the effector mechanisms for reactions of cell-mediated immunity.
POKEWEED MITOGEN-, CONCANAVALIN A-, AND PHYTOHEMAGGLUTININ-INDUCED DEVELOPMENT OF CYTOTOXIC EFFECTOR LYMPHOCYTES
Authors: Kirchner Holger , Blaese R. Michael
Published: June 2004

Cultures of chicken lymphoid tissues were tested for their capacity to lyse 51Cr-labeled chicken, burro (BRC), and human red blood cells (HRC) in the presence of phytomitogens. PHA-stimulated cultures lysed all three types of targets, while PWM and Con A showed a "target cell specificity" for HRC and BRC, respectively. In mixtures of target cells only the appropriate targets were lysed by lymphocytes activated by either Con A or PWM indicating that soluble lymphotoxins do not play a major role in these reactions. Preincubation experiments suggested that there may be a population of pre-existing aggressor cells which only require linking to the targets by the mitogens for activation of their cytotoxic potential.

Strong cytotoxic reactions were found with spleen cells, peripheral blood leucocytes, and bone marrow cells. Thymocytes were less active but could be stimulated for significant cytotoxicity, while bursal cells were generally unreactive. Spleen cells from agammaglobulinemic chickens totally lacking serum immunoglobulins and B cells with surface-bound immunoglobulins were as active as cells from normal chickens. The activity of spleen cells, from which phagocytic cells were removed was also unimpaired. These results indicate that the development of cytotoxic effector lymphocytes in mitogen-treated leucocyte cultures is a property of T lymphocytes. Although bone marrow cells fail to proliferate in response to these phytomitogens, they do have strong cytotoxic reactivity suggesting that different subsets of thymic-derived lymphocytes are responsible for mitogen-induced transformation and mitogen-induced cytotoxicity.
STUDIES ON MEMBRANE-BOUND RECEPTORS FOR ANTIGEN
Authors: Stout Robert D. , Coons Albert H.
Published: June 2004

The effect of polyadenylic: polyundylic acid complexes (poly A:U) on the amount of antibody on the surface of various populations of mouse lymphoid cells has been investigated by means of a sensitive measure of such activity—the binding by primed cell populations of ß-galactosidase (ßGZ) as an antigen. The sensitivity derives from the liberation of fluorescein from an artificial substrate, fluorescein-di-ß-galactopyranoside (FDßG). After incubation with 100 ng/ml of poly A:U, only 40% of the cells previously showing antigen-binding were still active. The optimum range of activity lay between 0.01–1.0 µg/ml poly A:U. Such cells showed increased RNA and protein synthesis as indicated by [3H]uridine and [14C]amino acid incorporation. The polynucleotide effect was abolished by incubation of the cells with sodium azide or iodoacetate, but not by puromycin. When the proteins on the cell surface were labeled by 125I, poly A:U caused their release into the medium.

Reports by others that the enhancing effect of polynucleotides on the immune response involves the adenylcyclase system are consistent with the finding reported here that reduction of binding by dibutryl 5'-cyclic monophosphoric acid (cAMP) and poly A:U were parallel in extent, and that theophylline and poly A:U acted synergistically in suboptimal concentrations of each.
SERUM-MEDIATED LEUKEMIA CELL DESTRUCTION IN AKR MICE
Authors: Kassel Robert L. , Old Lloyd J. , Carswell Elizabeth A. , Fiore Nancy C. , Hardy William D.
Published: June 2004

AKR mice with spontaneous leukemia were infused with normal serum from a variety of species. Leukemia cell destruction was produced by serum from strains of mice possessing the full spectrum of complement components, but not by serum from strains with a genetically determined deficiency of C5. Serum from guinea pigs, horses, and humans also causes destruction of leukemia cells. The antileukemic factor in normal serum was heat labile (56°C for 35 min) and could be inactivated by cobra venom factor (CVF). Tests of individual complement factors from guinea pig serum and from human serum suggest that C5 is the antileukemic complement component in normal serum. Evidence was obtained that complement also plays a role in the antileukemic effect of interferon and endotoxin.
DIFFERENTIATION OF T-CELL PRECURSORS IN NUDE MICE DEMONSTRATED BY IMMUNOFLUORESCENCE OF T-CELL MEMBRANE MARKERS
Authors: Loor F. , Kindred B.
Published: June 2004

When the thymus from an AKR mouse (TL-, θ-AKR) is grafted to a BALB/c-nu/nu mouse (TL2, θ-C3H), the grafted thymus is rapidly repopulated by host lymphocytes, i.e., lymphocytes having the TL2 and θ-C3H T-lymphocyte membrane antigen markers. θ-C3H lymphocytes also appear rapidly in the spleen and lymph nodes. After a few weeks, BALB/c nude mice grafted with AKR thymus and normal BALB/c mice could not be distinguished on the basis of the number of TL-positive thymocytes or θ-C3H-positive lymphocytes in thymus, spleen, or lymph nodes.

These experiments give a definitive proof of the existence of precursor cells for the T compartment of the lymphoid system in the nude mouse. They strongly suggest the involvement of host-derived T cells in the recovery of some T-cell functions by nude mice grafted with allogeneic thymuses.
IDIOTYPIC SPECIFICITY OF RABBIT ANTIBODIES TO STREPTOCOCCAL GROUP POLYSACCHARIDES
Authors: Braun Dietmar G. , Kelus Andrew S.
Published: June 2004

Anti-idiotypic antisera against six restricted rabbit streptococcal group specific antibodies have been raised in rabbits matched for allotypes. All these antisera reacted specifically with their homologous idiotypes on double-diffusion tests in agarose gel. In addition, they showed a high incidence of cross-specificities with group-specific hyperimmune sera induced in both closely related and unrelated individuals. These precipitating cross-specificities could be explained for two systems by the interference of rheumatoid factor.

Two idiotypic antibody systems have been analyzed in detail; these were restricted antibodies produced in a father and in one of his offspring. The methods employed included binding inhibition of radio-labeled homologous Fab fragments and hemagglutination inhibition with homologous idiotypic coat. The data demonstrated that only related rabbits produced, besides non-cross-reacting antibodies, idiotypically similar antibodies raised to the same antigen. About one-third of the cross-reactive idiotypes showed binding inhibition between 31 and 92%. Inhibition of binding above 50% in the paternal idiotypic system was only achieved by one offspring antibody whereas the F1 progeny idiotypic system was inhibited to this extent by seven antibodies of related rabbits. In contrast, 87.5% and 91.7% of antibodies of unrelated rabbits were less than 20% inhibitory.

Within this study two idiotypically identical antibodies have not been found. This implies that A-variant-specific antibodies of related rabbits which produced antipolysaccharide antibodies were structurally different. Cross-reaction, even if greater than 90% by binding inhibition, appears to involve only part and not all of the variable regions.
GRAFT-VS.-HOST REACTION IN TISSUE CULTURE
Authors: Auerbach Robert , Shalaby M. R.
Published: June 2004

The primary purpose of this study has been to validate the in vitro graft-vs.-host reaction as an experimental system. Time-dose studies have been presented for cells obtained from spleen, thymus, cortisone-treated thymus, inguinal lymph node, mesenteric lymph node, thoracic duct, and bone marrow cells. Both the degree of splenomegaly and the onset of spleen enlargement were found to be dependent on the number and source of cells tested.

The effect of several immunosuppressive agents was examined. Amantadine was found to suppress completely the graft-vs.-host reaction in vitro when present at a concentration of 75 µg/ml. Pretreatment of effector cells with mitomycin C prevented their subsequent ability to cause a graft-vs.-host reaction. The effect of X irradiation on immunocompetence of spleen cells in vitro paralleled the known effect of irradiation on in vivo immunocompetence.

Preimmunization did not increase the number or effectiveness of immunocompetent cells when measured under standard in vitro conditions. Preimmunization did, however, permit persistence of immunocompetence after immunosuppressive doses of X irradiation. Studies using congenic lines, moreover, indicated that the preimmunization effect could be demonstrated in strain combinations differing only in factors determined by the H-2 complex of genes.

A weak graft-vs.-host reaction could be detected in strain combinations not involving differences at the H-2 locus. The potential of the in vitro graft-vs.-host reaction as a highly reproducible, quantifiable, internally controlled, and experimentally accessible system for study of such critical problems as cell differentiation and cell interactions is discussed.
CROSS-STIMULATION OF MONOCLONAL ANTIBODIES IN ANAMNESTIC RESPONSES
Authors: Cramer Matthias , Braun Dietmar G.
Published: June 2004

Immunization of BALB/c mice with Group A streptococcal vaccines leads to the induction of high levels of monoclonal antibody populations. Subsequent immunization of these mice with Group A-variant streptococcal vaccines induces a significant level of monoclonal antibody of A-variant antigen specificity revealed by labeled group A-variant polysaccharide. During these course Av and Av' immunizations, the monoclonal Group A-specific antibodies were also restimulated to levels usually higher than the variant-specific antibodies. With two exceptions, these homogeneous antibody populations were not cross-reactive in vitro with the related antigen. Such cross-stimulation of monoclonal antibodies was interpreted as a function of particular membrane properties of the Ig receptor-bearing memory cells which, for restimulation, would only require the structurally closely related antigen which serves as a backbone to the original antigen, and not necessarily the exact fit of the homologous immunodominant group.
SPECIFIC MURINE B-CELL ACTIVATION BY SYNTHETIC SINGLE- AND DOUBLE-STRANDED POLYNUCLEOTIDES
Authors: Scher Irwin , Strong Douglas M. , Ahmed Aftab , Knudsen Richard C. , Sell Kenneth W.
Published: June 2004

The synthetic single- and double-stranded polynucleotides, poly I, poly C, and poly I·C, were shown to induce thymidine incorporation in six inbred strains of murine spleen cells. This stimulation was shown to be secondary to B-cell activation and not due to contamination of the polynucleotides with bacterial lipopolysaccharide (LPS). The ability of poly I·C to act as a B-cell mitogen, in addition to its behavior as a thymic-independent antigen, suggested that these two phenomena may be related. The similarity of the molecular structure of poly I·C to LPS, a material which also acts as a thymic-independent antigen and a B-cell mitogen, supports the hypothesis that the polyvalent nature of these materials accounts for their functional interaction with murine B cells.
INFLUENCE OF ERYTHROCYTE MEMBRANE COMPONENTS ON MALARIA MEROZOITE INVASION
Authors: Miller Louis H. , Dvorak James A. , Shiroishi Tsugiye , Durocher John R.
Published: June 2004

Chymotrypsin- and Pronase-treated human erythrocytes were refractory to invasion by P. knowlesi merozoites; invasion was not inhibited by trypsin or neurammidase treatment. These data implicate a surface protein other than sialoglycoprotein as the receptor site for merozoites. Invasion of rhesus erythrocytes was unaffected by pretreatment with these enzymes. Differences in membrane structure of erythrocytes from various species may explain the absence of an enzyme effect on rhesus erythrocytes.
DUAL REGULATORY ROLE OF THE THYMUS IN THE MATURATION OF IMMUNE RESPONSE IN THE RABBIT
Authors: Taniguchi Masaru , Tada Tomio
Published: June 2004

Rabbits thymectomized in early adulthood produced more antihapten antibody than sham-thymectomized controls after hyperimmunization with 2,4-dinitrophenyl bovine gamma globulin (DNP-BGG). The average associated constant of anti-DNP antibody produced by thymectomized animals was more than 10 times higher than that of the controls. Similar effects were obtained by extensive treatment of rabbits with antithymocyte serum (ATS) before and during the immunization with DNP-BGG. The results indicated that relative diminution of thymus-derived lymphocytes (T cells) resulted in a stimulation of antibody-forming cells with a higher affinity.

On the other hand, preimmunization of rabbits with different doses of BGG caused either enhancement or suppression of the hapten-specific antibody response, depending on the priming dose of BGG. The suppressed antibody response was always associated with a marked decrease in the antibody affinity. If rabbits were partially tolerized with a large dose of soluble BGG, some of the animals produced little antibody against hapten (DNP) coupled to this carrier, and the affinity of produced antibody was low. However, other rabbits tolerized with BGG produced large amounts of anti-DNP antibody upon hyperimmunization with DNP-BGG, whose affinity was only slightly lower than that of the control.

These results can be harmonized if it is assumed that the thymus plays an important role in the maturation of the immune response. It is postulated that T cells, in numbers ordinarily available, would first assist in the proliferation of antihapten antibody-forming cell precursors already selected by antigen, thus accounting for the rapid increase of antibody affinity in the early stage of immunization. However, after a larger number of carrier-specific T cells are made in response to continued immunization, these would suppress antibody-forming cells. The suppression would be greater for cells with higher affinity for antigen, resulting in a decrease in antibody affinity. This postulate explains preferential stimulation and suppression of cells having higher affinity receptors under circumstances in which T cell are relatively depleted or overstimulated, and further permits an explanation for the decrease of antibody affinity after long-term immunization.
A SEX-LINKED DEFECT IN THE CROSS-LINKING OF COLLAGEN AND ELASTIN ASSOCIATED WITH THE MOTTLED LOCUS IN MICE
Authors: Rowe David W. , McGoodwin Ermona B. , Martin George R. , Sussman Michael D. , Grahn Douglas , Faris Barbara , Franzblau Carl
Published: June 2004

A genetic abnormality in collagen and elastin cross-linking resembling experimental lathyrism has been identified in mice. The defect is an X-linked trait, attributed to the mottled locus which also influences coat color. The affected mice have aneurysms of the aorta and its branches, weak skin, and bone deformities in a spectrum of severity varying with the alleles at the mottled locus.

A defect in the cross-linking of collagen was demonstrated in the skin of the affected animals by a marked increase in collagen extractability and a reduced proportion of cross-linked components in the extracted collagen. A decrease in lysine-derived aldehyde levels was found in both skin collagen and aortic elastin similar to that found in lathyritic tissue. Furthermore the in vitro formation of lysine-derived aldehyde was reduced. Thus the cause of the connective tissue abnormalities in these mice appears to be a defect in cross-link formation due to an impairment in aldehyde formation.
MIXED LYMPHOCYTE REACTIVITY AGAINST NORMAL CELLS BY SPLENIC LYMPHOCYTES FROM TUMOR-BEARING MICE
Authors: Devlin R. G. , McCurdy J. D. , Baronowsky P. E.
Published: June 2004

The establishment of an intimate connection between autoimmunity and neoplasia would require the demonstration of an experimentally induced, tumor-dependent autoimmune process. For this reason, we have studied cellular immune reactions of mice bearing a transplantable leukemia (L1210). Spleen cells from hybrid BDF1 mice bearing the L1210 tumor (BDFt) reacted vigorously in mixed lymphocyte culture with mitomycin-treated, normal spleen cells from mice of the parental strain from which the L1210 tumor was derived (DBA/2). Spleen cells from nontumor-bearing BDF1 mice reacted only weakly with these parental cells. The BDFt cells likewise did not respond when cultured with mitomycin-treated spleen cells from the other parental strain (C57B1/6). The vigorous mixed lymphocyte reaction (MLR) by BDFt cells against normal parental cells of the same strain as the tumor was not due to a double exposure of the reacting cells to histocompatibility antigens shared by tumor cells and normal parental cells. The response of cells from tumor-bearing F1 mice against normal parental cells seen in these experiments suggests the possibility of the induction of an autoimmune-like process against host lymphocytes by spleen cells from leukemic mice. Theoretically such a phenomenon would considerably reduce an animal's ability to mount an immune attack against malignant cells.
THE ROLE OF PROPERDIN IN THE ALTERNATE PATHWAY OF COMPLEMENT ACTIVATION
Authors: Götze Otto , Müller-Eberhard Hans J.
Published: June 2004

Properdin (P), a highly basic euglobulin, was purified from human serum to molecular homogeneity without the use of zymosan. Isolated P was found to efficiently initiate activation of the alternate pathway of complement activation (C3 activator or properdin system) and to be an essential component during its early reaction stages. The activity of isolated P did not require the presence of an activating polysaccharide. It was therefore concluded that purified P had been obtained in an activated form (P).

In an isolated reaction system containing purified C3, C3 proactivator (C3PA), and C3 proactivator convertase (C3PAse), P was able to mediate the activation of C3PAse which in turn activated C3PA to cleave C3. This activation of C3PAse was found to depend on the presence of native C3. These results allowed the formulation of a concept in which P is envisaged to act as a modulator of native C3 enabling it to activate C3PAse.

Activation of C3 was efficiently mediated by P in the fluid phase. Efficient activation of C5, however, required the participation of an insoluble polysaccharide (zymosan). The possibility is raised therefore that P might also be an integral part of the multimolecular C5 convertase of the alternate pathway of complement activation.
RENAL HYPERTENSION IN RATS IMMUNIZED AGAINST ANGIOTENSIN I AND ANGIOTENSIN II
Authors: Oates Helen F. , Stokes Gordon S. , Storey Brian G. , Glover Robyn G. , Snow Beverley F.
Published: June 2004

Rats, actively immunized against angiotensin I (AI) and angiotensin II (AII), were subjected to unilateral renal artery constriction to determine whether the resulting hypertension, which may still ensue in the animal immunized against AII, could be prevented by such combined immunity.

Sustained immunity to both AI and AII neither changed preoperative blood pressures of the rats from those of control mock-immunized rats nor altered the incidence or severity of renal dip hypertension. Vascular hyperresponsiveness to small quantities of free angiotensin could not be invoked to explain the hypertension, for there was no significant difference between mock-immunized hypertensive animals, and those remaining normotensive, regarding pressor sensitivity to intravenous AI, AII, renin, and norepinephrine. (AI + AII)-immunized hypertensive rats required AI doses averaging 260 times greater than nonimmune hypertensives to elicit equipressor responses, and were refractory to renin, but not to norepinephrine.

Thus, while previous studies have not excluded direct participation of endogenous AI in renal clip hypertension in rats, evidence from our experiments makes it extremely difficult to sustain any pressor function therein for circulating AI or AII. Our results also preclude involvement of AII produced from circulating AI by conversion within arteriolar walls, close to receptor sites, since AI immunity would block this mechanism of action.
COMPLEMENT-DEPENDENT B-CELL ACTIVATION BY COBRA VENOM FACTOR AND OTHER MITOGENS?
Authors: Dukor Peter , Schumann Gebhard , Gisler Roland H. , Dierich Manfred , König Wolfgang , Hadding Ulrich , Bitter-Suermann Dieter
Published: June 2004

It has been proposed that two distinct signals are required for the triggering of the precursors of antibody-forming bone marrow-derived cells (B cells): (a) the binding of antigen or of a mitogen to the corresponding receptor sites on B-cell membranes and (b) the interaction of activated C3 with the C3 receptor of B lymphocytes. There is growing evidence that B-cell mitogens and T (thymus-derived cell)-independent antigens are capable of activating the alternate pathway of the complement system (bypass). Therefore, the effect of another potent bypass inducer was investigated with regard to B-cell activation and the role of C3. Purified, pyrogen-free cobra venom factor was mitogenic for both T and B lymphocytes (cortisone-resistant mouse thymus cells and lymph node lymphocytes from congenitally athymic mice). Venom factor could substitute for T cells by restoring the potential of antibody formation to sheep red blood cells in mouse B-cell cultures supplemented with macrophages or 2-mercaptoethanol. Venom factor may be capable of conferring activated C3 to the C3 receptor of B lymphocytes: preincubation of lymphoid cells with homologous serum or plasma, 10 mM EDTA, and sepharose-coupled venom factor converted with serum to an enzyme active against C3, inhibited their capacity to subsequently form rosettes with sheep erythrocytes sensitized with amboceptor and C5-deficient mouse complement. In the absence of EDTA, preincubation of freshly prepared B-cell suspensions with C3-sufficient homologous serum also blocked their subsequent interaction with complement-sensitized erythrocytes and at the same time rendered them reactive to an otherwise T-cell-specific mitogen. Moreover, mitogen induced B-cell proliferation in lymph node (but not in spleen) cell cultures, appeared to depend on the availability of exogenous C3: zymosan-absorbed fetal bovine serum (only 8.3% site-forming units remaining) supported T-cell activation by phytohemagglutinin, concanavalin A, and venom factor, but failed to sustain B-cell stimulation by pokeweed mitogen, lipopolysaccharide, and venom factor. T-cell-dependent antibody formation in composite cultures containing T cells or T-cell-substituting B-cell mitogens, B cells, and macrophages, always required the presence of C3-sufficient serum.
ISOLATION AND CHARACTERIZATION OF C-TYPE VIRAL GENE PRODUCTS OF VIRUS-NEGATIVE MOUSE CELLS
Authors: Stephenson John R. , Tronick Steven R. , Reynolds Roberta K. , Aaronson Stuart A.
Published: June 2004

Antigens which immunologically cross-react with two mouse C-type viral polypeptides, p30 and p12, are present at very low levels in normal virus-negative mouse cells. These two antigens have been purified by 50–300-fold from cell extracts and shown to cochromatograph with the corresponding labeled viral polypeptides in several systems. Their type-specific antigenicities are shown to be distinct from those of previously tested MuLV isolates suggesting that they may be components of a new class of endogenous C-type virus. The methods utilized in the present studies for concentration of virus-specific antigens of normal mouse cells provide an approach for detection of C-type viral antigens in cells of other species.
INDUCTION OF IgG BY LIPID A IN THE NEWBORN MOUSE
Authors: Kolb Cornelia , Di Pauli Raimund , Weiler Eberhardt
Published: June 2004

IgG of paternal allotype first becomes detectable in the serum of (BALB/c x C57BL/6)F1 mice between day 12 and 14 after birth and reaches adult levels at an age of 5 wk. Since in mice there is a transfer of maternal IgG molecules through the placenta and via milk, F1 heterozygous at the allotype locus were used and the concentrations of IgG with paternal allotype were measured. This was done by a sensitive method capable of detecting IgG concentrations as low as 5 x 10–4 of normal adult serum levels. It is based on the quantitative inhibition of allotype-specific facilitation of hemolysis.

When lipid A or Salmonella bacteria were injected into neonatal mice, a stimulation of IgG synthesis was observed. Thus IgG levels were enhanced 10-30-fold compared to the nontreated mice. No increase in IgG levels was obtained in adult mice after treatment with lipid A. Whether the newborns were injected at birth, on day 2, 4, or 7, IgG was first demonstrable in the treated mice at an age of 6–11 days.

The increase in IgG levels was not paralleled by a demonstrable antibody activity against lipid A, SRBC, and LPS. Thus the bulk of newly induced IgG is probably a statistical distribution of different specificities.