bluuebunny/crossref_metadata_2025 huggingface dataset:
INDUCTION OF IMMUNOLOGICAL TOLERANCE TO A THYMUS-DEPENDENT ANTIGEN IN THE ABSENCE OF THYMUS-DERIVED CELLS
Authors: Schrader John W.
Published: June 2004

Specific immunological unresponsiveness was induced using thymus-dependent antigens in congenitally athymic (nu/nu) mice, in which no T-cell function has been demonstrated. The tolerance was induced in vivo by the injection of 5–10 mg of either FGG or DNP-HGG.

Spleen cells from treated mice were tested in vitro for the ability to mount thymus-independent immune responses against FGG in the presence of polymerized flagellin POL, and the DNP determinant conjugated to POL. A specific deficiency in either the in vitro anti-FGG or anti-DNP response was demonstrated, depending on the antigen used for treatment of the spleen cell donor. Athymic mice treated with FGG were also tested by in vivo challenge with FGG given with POL as an adjuvant and were found to be hyporesponsive.

Unresponsiveness to in vitro challenge was established by 24 h after the in vivo injection of FGG. It was found that the injection of POL with the FGG prevented the development of unresponsiveness, but not if the POL was given 24 h or more after the FGG.

The unresponsiveness could not be overcome by confrontation with allogeneic spleen cells from CBA mice, although the presence of allogeneic spleen cells had a large amplifying effect on the response of control spleen cells. These experiments demonstrate a mechanism for the tolerization of bone marrow-derived cells by thymus-dependent antigens in the absence of the thymus.
CONCORDANT SEGREGATION OF THE EXPRESSION OF SV40 T ANTIGEN AND HUMAN CHROMOSOME 7 IN MOUSE-HUMAN HYBRID SUBCLONES
Authors: Croce Carlo M. , Koprowski Hilary
Published: June 2004

Subcloning of Simian virus 40 (SV40) T antigen-positive mouse-human hybrids, derived from the fusion of mouse cells deficient in thymidine kinase with SV40-transformed Lesch Nyhan fibroblasts, resulted in their segregation into T antigen-positive and negative subclones. Positive correlation between the presence of human chromosome 7 and the expression of SV40 T antigen was established in the subclones examined. These results negate the possibility of a transfer of the SV40 genome to a mouse chromosome.
THE MEDIATOR OF CELLULAR IMMUNITY
Authors: McGregor D. D. , Logie Pamela S.
Published: June 2004

Peritoneal exudates induced in rats infected with Listeria monocytogenes contain sensitized lymphocytes which can protect normal recipients against a Listeria challenge. The protective cells arise in lymphoid tissue remote from the peritoneal cavity. Those formed in the caudal lymph nodes of subcutaneously infected rats are delivered to the thoracic duct and hence to the blood from where they are drawn into exudates. Immunoblasts are the most immature members of this protective cell population and they alone among the cells in central lymph localize in exudates induced by killed bacteria. They do so in substantial numbers, but only during the early postinduction period.

The "homing" of immunoblasts to inflammatory foci seems to be determined by a general property of the cells rather than their immunological commitment; however, the intense inflammation induced by organisms to which an animal has been specifically sensitized is accompanied by an exuberant influx of immunoblasts into lesions. Sensitized lymphocytes that extravasate in the inflamed peritoneal may generate more of their own kind, but some give rise to small lymphocytes. The latter also have protective properties and, with time, comprise an increasing portion of the protective cell population.

The results imply that the tissue disposition of sensitized lymphocytes in the body is determined by a complementary relationship between blood-borne immunoblasts and vascular endothelium in inflamed tissue. The results also provide a plausible explanation for the concentration of sensitized lymphocytes at sites of microbial implantation where they alone would be expected to collaborate with monocyte-derived macrophages in the control of infection.
GENETICS OF RESTRICTED ANTIBODIES TO STREPTOCOCCAL GROUP POLYSACCHARIDES IN MICE
Authors: Cramer Matthias , Braun Dietmar G.
Published: June 2004

The immune response of nine inbred and one outbred strain of mice to the streptococcal group A polysaccharide was investigated with respect to magnitude and restriction. Analytical isoelectric focusing served as a tool to estimate the degree of restriction of Group A polysaccharide-specific antibodies.

It proved feasible to distinguish low and intermediate from high responder strains, and to delineate strain-specificity of isoelectric focusing spectra of the immune sera. For example, immune sera of BALB/c mice, restricted high responders, and of C57BL/6 mice, heterogeneous low responders, had distinct focusing properties.

Responsiveness was a dominant autosomal genetic trait in C57BL/6 x BALB/c F1 hybrid mice, irrespective of the maternal and the paternal genotype; the immune sera of these mice had their own, rather uniform isoelectric focusing spectra whereby structural genes of the low responder strain were expressed to predominant levels in 81% of the hybrids.

Responsiveness in C57BL/6 x BALB/c F2 progeny segregated into 79% high and 21% low responders, and showed no genetic linkage to the following characteristics: hair color, sex, H-2 type, and Ig allotype of the heavy chain. The isoelectric focusing properties of these immune sera indicated segregation into patterns like BALB/c mice (40%), F1 hybrids (48%), and C57BL/6 mice (12%). Since this segregation is independent of any of the above criteria in these F2 mice a regulatory gene(s) is postulated that controls the clonal pattern of the immune response.
CELLULAR INTERACTIONS IN THE PROLIFERATIVE RESPONSE OF HUMAN T AND B LYMPHOCYTES TO PHYTOMITOGENS AND ALLOGENEIC LYMPHOCYTES
Authors: Lohrmann Hans-Peter , Novikovs Ligita , Graw Robert G.
Published: June 2004

In vitro studies were performed to determine the proliferative responsiveness of human peripheral blood thymus-dependent (T) and thymus-independent (B) lymphocytes to phytomitogens and allogeneic lymphocytes. Recombination of T and B cells, with selective inhibition of proliferation of one of the two populations, was used to identify cellular interactions which may contribute to cell proliferation. The distinctive feature of human T lymphocytes to form rosettes with unsensitized sheep erythrocytes was utilized to separate human peripheral blood lymphocytes into highly purified resetting (T) and non-rosetting (B) cells. The proliferative response of these separated lymphocyte subpopulations to various stimulants was assessed from the uptake of tritiated thymidine into DNA.

Phytohemagglutinin, concanavalin A, pokeweed mitogen, and allogeneic lymphocytes stimulated separated T cells, whereas no proliferation was observed with the T-cell-depleted B-cell population. This suggests that it is the human T cell which is activated directly by these stimulants. In the presence of T cells (proliferating or nonproliferating), B cells were capable of proliferation following stimulation with phytomitogens, but not in response to histocompatibility antigens. Thus, T-cell-mediated B-cell proliferation contributes to the overall lymphocyte response in phytomitogen-stimulated T + B cell mixtures, but not in human mixed leukocyte cultures. T-cell activation by allogeneic cells required the presence of monocytes; in contrast, the three tested phytomitogens stimulated T cells in the absence of monocytes. This indicates that direct interaction of mitogens with lymphocyte membrane receptors is sufficient to trigger T cells into proliferative response. However, monocytes considerably enhanced the proliferative response of T cells in a dose-dependent fashion; this monocyte-dependent mechanism of T-cell activation was predominant at lower concentrations of phytomitogens, and contributed relatively less at higher mitogen doses. Both, the direct, monocyte-independent, and the indirect, monocyte-dependent T-lymphocyte activation contribute to the total in vitro response of lymphocyte preparations to phytomitogens.
SELECTIVE TRIGGERING OF HUMAN T AND B LYMPHOCYTES IN VITRO BY POLYCLONAL MITOGENS
Authors: Greaves Melvyn , Janossy George , Doenhoff Michael
Published: June 2004

Human lymphocytes from spleen and tonsils have been cultured with a variety of polyclonal mitogens. Cultures consisted of either unseparated T and B cells or alternatively purified T or B lymphocytes. The purity of the starting cell populations and the origin of activated lymphoblasts was analyzed with a panel of seven markers which discriminate between T and B cells. The selectivity of the lymphocyte responses was influenced by cell populations in a given culture, the mitogen used, and to a limited extent on culture conditions. Purified T lymphocytes from tonsil and spleen responded to phytohemagglutinin (PHA), pokeweed mitogen (PWM), and staphylococcal enterotoxin B (SEB). Purified B cells from spleen responded well to PWM, weakly to SEB and lipopolysaccharide, but not at all to PHA. Tonsil B cells responded weakly to PWM and SEB but not to PHA. Some B lymphocytes do respond to PHA in the presence of activated T cells. These results are discussed in relation to previously reported selective responses of human cells and parallel studies in animal species.
ROLE OF MENINGOCOCCAL ENDOTOXIN IN MENINGOCOCCAL PURPURA
Authors: Davis Charles E. , Arnold Karen
Published: June 2004

Enteric bacilli and meningococci (MGC) both contain potent endotoxins, but purpuric skin lesions indistinguishable from the experimental dermal Shwartzman reaction are much more common during meningococcal bacteremia than during bacteremia with enteric organisms. Highly purified lipopolysaccharides (LPS), virtually free of contamination by protein, RNA, and capsule, were extracted by a modification of the phenol-water technique from MGC (serogroups A, B, and C) and enteric bacilli (Escherichia coli 04 and 0:111, and Salmonella typhimurium). Polysaccharides in these LPS were similar by gas chromatography except for one galactose-deficient strain of MGC (135B).

LPS from MGC and enterics were equally potent for the general Shwartzman reaction and mouse lethality, but LPS from MGC was 5–10 times more potent in inducing the dermal Shwartzman reaction. The greater skin potency of LPS from MGC explains the prominence of purpura in meningococcemia. Comparison of the properties of LPS may explain other differences in clinical syndromes caused by gram-negative bacteria.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Benacerraf Baruj , Kapp Judith A. , Pierce Carl W. , Katz David H.
Published: June 2004

The conditions for cooperative interactions between nonresponder B10.S B cells and GAT-primed irradiated (C57BL/6 x SJL)F1 T cells in the response by cultures of mouse spleen cells to GAT were investigated. GAT-specific antibody responses could be elicited by soluble GAT in cultures of GAT-primed irradiated (C57BL/6 x SJL)F1 T cells with C57BL/6 B cells but not with B10.S B cells.

In contrast, when GAT was presented to the cultures on F1 macrophages or as aggregates of GAT with MBSA, GAT-specific PFC responses were observed with both B10.S or C57BL/6 B cells. Irradiated GAT-primed T cells were nevertheless essential for the development of these responses. The GAT-specific response of B10.S B cells in these cultures was inhibited by the addition of soluble GAT at culture initiation. These results indicate that genetic disparity at Ir loci is not an absolute barrier to T-B-cell cooperative interactions in the response to antigens under Ir gene control. The significance of these data for the function of Ir gene products in immunocompetent cells is discussed.
SELECTIVE ROLES OF THYMUS-DERIVED LYMPHOCYTES IN THE ANTIBODY RESPONSE
Authors: Takemori Toshitada , Tada Tomio
Published: June 2004

Passive transfer of thymocytes and spleen cells from donors primed with keyhole limpet hemocyanin (KLH) caused significant decrease in the average avidity of anti-DNP antibodies produced by direct and indirect PFC in the recipients in both primary and adoptive secondary antibody responses against DNP-KLH. The analysis of the avidity distribution of antibodies produced by plaque-forming cells (PFC) indicated that the observed decrease in the average avidity is primarily due to the selective loss of high avidity subpopulation of PFC leaving low avidity subpopulation relatively unaffected. The degree of suppression in antibody avidity did not correlate with the reduction in the number of PFC, and thus causing the "shift" of avidity distribution of PFC to the low avidity end. These results indicate that the "maturation" of antibody in the T-cell-dependent antibody response is influenced by the carrier-specific suppressor T cells with respect to the emergence and selection of B cells having high affinity receptors for hapten. It is suggested that B cells binding antigen with high affinity receptors would be more easily affected than those with low affinity receptors by specific suppressor T cells which are capable of reacting the carrier portion of the same antigen.
SEPARABLE POPULATIONS OF ACTIVATED THYMUS-DERIVED LYMPHOCYTES IDENTIFIED IN TWO ASSAYS FOR CELL-MEDIATED IMMUNITY TO MURINE TUMOR ALLOGRAFTS
Authors: Tigelaar Robert E. , Gorczynski R. M.
Published: June 2004

The immune response of C57BL mice to a DBA/2 tumor allograft has been assessed in two assays of cell-mediated immunity, the in vitro lysis of 51Cr-labeled target cells and the antigen-mediated inhibition of macrophage migration. Both assays were shown to be measuring a T-cell-mediated reaction. Three types of experiments suggested that distinct subpopulations of T cells mediate these reactions. The tissue distributions of these activities was distinctive; both activities were present in spleens from i.p. immunized mice, but only macrophage migration inhibition activity was found in the peripheral lymph nodes (PLN) of such mice. Adoptive transfer of immune spleen cells into irradiated syngeneic recipients revealed that while a substantial amount of migration inhibition activity could subsequently be found in PLN, cytotoxic activity was found predominantly in the spleens of these adoptive hosts. Velocity sedimentation analysis of immune cells 14 days after i.p. immunization indicated that while the majority of cytotoxic activity was associated with small and medium lymphocytes, the majority of migration inhibition activity was associated with medium and large lymphocytes. In addition, normal spleen cells were fractionated by velocity sedimentation immediately before allosensitization in vitro. Subsequent analysis of the sensitized fractions revealed that the activity profiles for cytotoxicity and macrophage migration inhibition were not coincident. The implications of these observations are discussed.
ALLOANTISERUM-INDUCED INHIBITION OF MIGRATION INHIBITION FACTOR PRODUCTION IN IMMUNE RESPONSE GENE-CONTROLLED IMMUNE SYSTEMS
Authors: Ben-Sasson Shlomo Z. , Shevach Ethan , Green Ira , Paul William E.
Published: June 2004

We have previously demonstrated that alloantisera prepared by reciprocal immunization of strain 2 and strain 13 guinea pigs specifically block stimulation of in vitro DNA synthesis in genetically controlled systems. In order to determine whether this blockade extends to other T-lymphocyte functions, we examined the effect of alloantisera on the production of migration inhibition factor (MIF). (2 x 13)F1 guinea pigs were immunized with a DNP derivative of the copolymer of L-glutamic acid and L-lysine (DNP-GL) and with DNP guinea pig albumin (GPA). The response to the former is controlled by a 2-linked Ir gene while that to the latter is mainly controlled by a 13-linked Ir gene. MIF production was assayed by an indirect procedure in which the migrating cell population lacked the histocompatibility antigen against which the alloantiserum was directed. Our results showed that anti-2 serum blocked MIF production by F1 cells in response to DNP-GL but not DNP-GPA while anti-13 serum had the opposite effect. These experiments show that expression of a second major T-cell function is specifically blocked by alloantisera and suggest that Ir-gene products may act as antigen recognition substances on more than one type of T cell.
THE DIFFERENTIATION PATHWAY OF T LYMPHOCYTES
Authors: Matter Alex
Published: June 2004

Two experimental models have been used to study T-cell differentiation. The first, a graft-vs.-host reaction, was induced by injecting thymocytes or cortisone-resistant thymocytes into lethally irradiated allogeneic mice. The second was tumor graft rejection in allogeneic hosts. Ultrastructural studies at various time intervals revealed two differentiated T-cell types. One of these (the "pale" cell) is probably high cytotoxic as measured in the chromium-release assay, the other (the "dark" cell) may be an "amplifier" cell, helping in the differentiation of cytotoxic cells.
CONCANAVALIN A BINDING PROTEINS OF LYMPHOID CELL SURFACE
Authors: Choi Yong Sung , Jenson James C.
Published: June 2004

A Concanavalin A binding protein of chicken lymphoid cells was isolated by affinity chromatography of intact lymphoid cells. This protein with a mol wt of 160,000 daltons revealed two peptides (30,000 and 20,000 daltons) in SDS-acrylamide gel electrophoresis.
IgM-PRODUCING TUMORS IN THE BALB/c MOUSE
Authors: Andersson Jan , Buxbaum Joel , Citronbaum Ronald , Douglas Steven , Forni Luciana , Melchers Fritz , Pernis Benvenuto , Stott David
Published: June 2004

Five adjuvant induced BALB/c tumors producing IgM—McPc 1748, W 3469, TEPC 183, McPc 774, and Y 5781—were characterized morphologically by electron microscopy, analysis of the distribution of surface-bound and intracytoplasmic IgM using immunofluorescence, and by biochemical study of IgM synthesis, turnover, and secretion. The cells of different tumors appear to represent different stages in B-cell maturation when compared to normal, lipopolysaccharide-stimulated B cells. Thus, McPc 1748 tumor cells resemble 10–25-h stimulated normal B cells, 3469 cells resemble 20–35-h stimulated B cells, TEPC 183 cells resemble 45–65-h stimulated B cells, Y 5781 cells resemble 80–110-h stimulated B cells, and McPc 774 cells resemble 100–130-h stimulated B cells.
RESTORATION OF CELL-MEDIATED IMMUNITY TO ANIMALS BLOCKED BY A HUMORAL RESPONSE
Authors: MacKaness George B. , Lagrange Philippe H.
Published: June 2004

The T cells which mediate delayed-type hypersensitivity (DTH) to sheep red blood cells (SRBC) are blocked by a normal humoral response and cannot be made to function by further immunization. They can be rescued to some extent by treatment with immunopotentiating agents such as cyclophosphamide (CY) which suppresses the antibody response selectively, or by BCG which interferes with the action of serum blocking factors. These two agents together can restore cell-mediated immunity completely, but a further antigenic stimulus is needed to reestablish DTH in mice blocked by a long period of continuous exposure to SRBC.
THE EFFECT OF CELLS TRANSFERRED INTO THE MOUSE BLASTOCYST ON SUBSEQUENT DEVELOPMENT
Authors: Brinster R. L.
Published: June 2004

Bone marrow cells from CBA T6T6 mice and testicular teratocarcinoma cells from 129 SvSl mice were transferred into blastocysts from random-bred Swiss albino mice. The blastocysts were allowed to develop in foster mothers and the adults resulting from these blastocysts were studied for evidence of an effect of the transferred cells. A total of 137 adults resulted from the experiments, and one of the mice that had received teratocarcinoma cells in the blastocyst stage showed several thin stripes of agouti hair. All the adult animals received grafts of skin from animals identical to those supplying the cells. In all cases the animals that resulted from blastocysts into which cells had been transferred maintained skin grafts for a significantly longer period than controls. In a number of cases the graft developed agouti hair and in two cases the graft was maintained for approximately 2 mo. These experiments indicate that the transferred cells were able to establish small colonies in the embryos and that some of these cells persisted into the adult.
THE STRUCTURAL BASIS FOR BINDING OF COMPLEMENT BY IMMUNOGLOBULIN M
Authors: Hurst Mary M. , Volanakis John E. , Hester Raymond B. , Stroud Robert M. , Bennett J. Claude
Published: June 2004

An insight into the structural features of human IgM that are responsible for its capacity to bind the first component of complement (C) has been obtained by examining the ability of IgM subfragments to bind active C1 (C1). The smallest two fragments found to bind C1 were the major CNBr fragment of the Fc portion of IgM and the CH4 fragment of the carboxy-terminal domain. The smallest fragment which fixes C1 has a disaggregated mol wt of 6,800, consists of 60 residues, and contains no carbohydrate. Structural considerations and sequence overlaps suggest that the amino-terminal side of the CH4 domain (24 amino acid residues) might be responsible for fixing C1.
HUMAN T LYMPHOCYTE "E" ROSETTE FUNCTION
Authors: Chisari Francis V. , Edgington Thomas S.
Published: June 2004

The capacity of normal human T lymphocytes to form rosettes with sheep red blood cells can be inhibited by drugs or agents which induce elevations in intracellular levels of cyclic AMP. The effect is early in the presence of agents which elicit rapid elevations in intracellular cyclic AMP (isoproterenol, aminophylline) and occurs later in the presence of cholera toxin which induces a dalayed increase in endogenous cyclic AMP. Dibutyryl cyclic AMP is inhibitory, and the effects of dibutyryl cyclic AMP and the adenyl cyclase stimulators are potentiated by inhibition of phosphodiesterase. These data provide substantial evidence that elevation of intracellular cyclic AMP diminishes E rosette function of lymphocytes.
MEMBRANE IMMUNOGLOBULINS OF B LYMPHOCYTES
Authors: Fu S. M. , Kunkel H. G.
Published: June 2004

Hemagglutination and fluorescent antibody studies have provided strong evidence for the unavailability or absence of specific antigenic sites on membrane-bound IgM which are present in serum and intracellular IgM. Antisera specific for different parts of the molecule indicated that a portion but not all of the Fc was involved. Absorption experiments with normal and leukemic viable B lymphocytes failed to remove a population of Fc antibodies found in IgM-specific antisera. Similar findings were made for IgD, the other major membrane immunoglobulin of human peripheral blood B cells. Various interpretations of these observations are discussed. The most likely possibility appears that the C-terminal portion of the heavy chains of the immunoglobulin molecule is buried in the membrane.
IMMUNE RESPONSES IN VITRO
Authors: Pierce Carl W. , Kapp Judith A. , Solliday Susan M. , Dorf Martin E. , Benacerraf Baruj
Published: June 2004

The effects of alloantisera against leukocyte alloantigens on plaque-forming cell (PFC) responses to sheep erythrocytes and the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) by mouse spleen cells in vitro have been investigated. Polyspecific antibodies against both H-2 and non-H-2 alloantigens on responding spleen cells suppressed both IgM and IgG PFC responses; antisera against alloantigens coded for by the K and I regions, but not the D region, of the H-2 complex also effectively suppressed PFC responses. The suppression was not due to cytotoxicity to the spleen cells or anti-immunoglobulin activity in the sera and was directly related to the amount of antiserum added to the cultures. The suppression was specific for spleen cells against which the alloantiserum was directed. The alloantisera suppressed responses most effectively when present during the first 24 h of incubation, and although not rendering lymphoid cells incapable of developing PFC responses after removal of noncell-bound antibody, did act by interfering with successful initiation of the PFC response. The alloantisera suppressed both IgM and IgG PFC responses when directed against alloantigens only on macrophages, but selectively suppressed IgG responses when directed against alloantigens only on lymphoid cells. The alloantisera did not interfere with the ability of macrophages to bind GAT or to support the viability of the lymphoid cells, but did interfere with the ability of macrophage-associated antigen to effectively stimulate antibody responses by the lymphoid cells. Possible mechanisms for the effects of alloantisera on macrophages and the selective suppression of IgG responses when the antisera are directed against alloantigens on lymphoid cells are discussed with reference to our current understanding of genetic restrictions governing cell interactions in the development of antibody responses in mice.
STUDIES ON THE MECHANISM OF ENDOGENOUS PYROGEN PRODUCTION
Authors: Bodel Phyllis
Published: June 2004

The characteristics of pyrogen production and release by human blood monocytes were investigated. A dose-response assay of monocyte pyrogen in rabbits indicated a linear relationship of temperature elevation to dose of pyrogen at lower doses. Monocytes did not contain pyrogen when first obtained, nor did they release it spontaneously even after 5 days of incubation in vitro. Pyrogen production was apparent 4 h after stimulation by endotoxin or phagocytosis, and continued for 24 h or more. Puromycin, an inhibitor of protein synthesis, prevented both initiation and continuation of pyrogen production and release. Pyrogen-containing supernates retained most pyrogenic activity during overnight incubation even in the presence of activated cells. Lymphocytes appeared to play no role in either initiation or continuation of pyrogen production in these studies.
TUMOR INDUCTION BY MURINE SARCOMA VIRUS IN AKR AND C58 MICE
Authors: Chieco-Bianchi Luigi , Colombatti Alfonso , Collavo Dino , Sendo Fujiro , Aoki Tadao , Fischinger Peter J.
Published: June 2004

Adult AKR and C58 mice injected intramuscularly with murine sarcoma virus, Moloney isolate (M-MSV), developed high incidence of nonregressing local tumors. Histologically, these tumors revealed the typical pleomorphism of M-MSV sarcomas; in some cases, however, neoplastic tissue showed a nodular or diffuse growth of monomorphic myoblastlike cells, reminiscent of clonal aggregates. No depression of immune reactivity was found in M-MSV-injected mice as evaluated by direct hemolytic plaque-forming cells against SRBC and by virus-neutralizing antibody production.

The MSV recovered from the induced tumors proved to be, by neutralization assay, a Gross (G)-MSV pseudotype. Moreover, tumor cell suspensions absorbed out cytotoxic antibody directed against G-cell surface antigens. Therefore, the conclusion was drawn that MSV with envelope characteristics of endogenous G leukemia virus had formed in vivo through a phenotypic mixing phenomenon. The failure of tumors to regress has been interpreted as mainly due to the partial unresponsiveness of host immune reactivity towards G-MuLV specified antigens.

Since MSV-tumors arose in AKR mice after a very long latent period, the possibility was considered that this relative resistance might depend on immunologic mechanisms. In fact, M-MSV-injected AKR mice immunodepressed by goat antimouse lymphocyte serum or rendered partially tolerant by neonatal M-MuLV inoculation developed sarcomas with higher incidence and with a shorter latency. Furthermore, the MSV recovered from these early tumors proved to be the original Moloney pseudotype.
SOMATIC CELL HYBRIDS BETWEEN MOUSE PERITONEAL MACROPHAGES AND SV40-TRANSFORMED HUMAN CELLS
Authors: Croce Carlo M. , Koprowski Hilary
Published: June 2004

Fusion of mouse peritoneal macrophages with SV40-transformed human cells, deficient in hypoxanthine guanine phosphoribosyltransferase, resulted in the formation of transformed somatic cell hybrids which contained, without exception, the human chromosome 7 carrying the SV40 genome. It is postulated that the hybridization of mouse nondividing cells with human cancer cells could permit the identification of the human "oncogenic" chromosome(s) present in human cancer cells, since such chromosome(s) should be retained by the totality of the mouse-human hybrid cells.
A SYNTHETIC GLYCOLIPID WITH B-CELL MITOGENIC ACTIVITY
Authors: Rosenstreich David L. , Asselineau Jean , Mergenhagen Stephan E. , Nowotny Alois
Published: June 2004

A synthetic glycolipid, N-palmitoyl-D-glucosamine, (NPG) was found to be a potent B-cell mitogen, that stimulated spleen cells from nu/nu as well as from normal mice. The proper dispersion of the water insoluble preparation is critical for the elicitation of this mitogenic effect. Limulus lysate clotting assay indicated that the NPG preparation either contains only 0.001% endotoxin contamination, or that NPG itself is 10–5 times less active in this assay than purified endotoxic LPS. Since such low levels of endotoxin concentration are not mitogenic, it is concluded that synthetic N-palmitoyl-D-glucosamine, when properly dispersed, is itself a B-cell mitogen.
ANTIBODY RESPONSES TO ANTIGENIC DETERMINANTS OF INFLUENZA VIRUS HEMAGGLUTININ
Authors: Virelizier Jean-Louis , Postlethwaite Roy , Schild Geoffrey C. , Allison Anthony C.
Published: June 2004

Using immunodiffusion methods it has been shown that purified hemagglutinin (HA) extracted from two related strains of influenza A viruses (A/PR8/34 and A/FM1/47) have two distinct antigenic determinants, or groups of determinants. One determinant is cross-reactive while the other is strain-specific. Antisera raised in normal mice against HA were shown to contain two populations of antibody molecules, each directed against one of the determinants. Immunization of thymus-deprived (TXBM) mice showed a strong thymus dependence of antibody formation to HA. However, the thymus dependence of antibody formation against the cross-reactive determinant could be overcome by repeated inoculations of HA in TXBM mice, indicating a different handling of two portions of the same molecule by the immunological system. Strong, secondary-type responses to the strain-specific determinant were observed in primed thymus-deprived mice after reconstitution with virgin thymus cells, showing that specific immunological memory was elicited by this determinant despite the absence of detectable antibody secretion. These findings are interpreted as examples of immunological recognition and memory mediated by B lymphocytes and discussed in terms of mechanisms of T and B lymphocyte co-operation. It is suggested that the helper effect of T lymphocytes is exerted at a late stage in the differentiation of specific populations of B cells into antibody-secreting cells.
ANTIBODY RESPONSES TO ANTIGENIC DETERMINANTS OF INFLUENZA VIRUS HEMAGGLUTININ
Authors: Virelizier Jean-Louis , Allison Anthony C. , Schild Geoffrey C.
Published: June 2004

Mice immunized sequentially with two related influenza virus hemagglutinins (HA) produced a secondary antibody response with two different specificities. Some antibodies were specific for determinants common to both HA's. Paradoxically, some antibodies were directed to determinants existing only in the HA first encountered. Primed spleen cells treated with anti-θ serum and complement were transferred from animals immunized with the first HA to either normal, irradiated, or thymus-deprived recipients. These memory cells were boosted in the recipients with either the homologous or the heterologous cross-reacting HA. B-memory lymphocytes were shown to be directly triggered by both HA's and to be able to secrete, independently of T lymphocytes, antibodies to both kinds of determinants. However, T cells were shown to modulate this secondary response by either enhancing or suppressing antibody secretion by B-memory cells, depending on experimental conditions. These results are discussed in terms of antigen recognition by B cells and of kinetics of development of immunological memory.
SUBSTRATES OF HAGEMAN FACTOR
Authors: Heck Louis W. , Kaplan Allen P.
Published: June 2004

Unactivated partial thromboplastin antecedent (PTA) has been purified by sequential chromatography of plasma on quaternary aminoethyl Sephadex, sulphoprophyl Sephadex, Sephadex G-150, and passage over an anti-IgG immunoadsorbant. The preparation gave a single band after alkaline disc gel electrophoresis, sodium dodecyl sulfate (SDS) gel electrophoresis and isoelectric focusing in acrylamide gels and was found to have a mol wt of 175,000 by gel filtration, 163,000 by SDS gel electrophoresis, and an isoelectric point of 8.8–9.4 (peak 9.0–9.1). Pre-PTA was activated directly by activated Hageman factor or by Hageman factor prealbumin fragments. Its coagulant activity was inhibited by DFP, soybean trypsin inhibitor and trasylol but not by lima bean trypsin inhibitor or ovomucoid trypsin inhibitor indicating that activated PTA possesses the same inhibition profile utilizing these reagents as does plasma kallikrein. A major plasma inhibitor of activated PTA was found to be a 65,000 mol wt α-globulin which was isolated free of α1-chymotrypsin inhibitor, inter α-trypsin inhibitor, α2-macroglobulin, and the other known inhibitors of activated PTA, the activated first component of complement (C1 INH), and antithrombin III. Its physicochemical properties were identical to α1-antitrypsin, and it was absent in α1-antitrypsin-deficient plasma thereby identifying this PTA inhibitor as α1-antitrypsin.
INDUCTION OF GUINEA PIG B-CELL LYMPHOKINE SYNTHESIS BY MITOGENIC AND NONMITOGENIC SIGNALS TO Fc, Ig, AND C3 RECEPTORS
Authors: Wahl S. M. , Iverson G. M. , Oppenheim J. J.
Published: June 2004

This study shows that bone marrow-derived lymphocytes of guinea pigs if appropriately activated produce a monocyte chemotactic factor (MNL CTX). Activation of B lymphocytes to produce a chemotactic lymphokine occurs subsequent to interactions with a variety of membrane-associated receptors. Polymeric B-cell mitogens with multiple binding sites, polymerized flagellin and lipopolysaccharide, initiated mediator synthesis. Furthermore, interaction of antigen-antibody complexes or aggregated gamma globulin with the Fc receptor and binding of antigen-antibody-complement complexes at the C3 receptor can effectively facilitate mediator production in the absence of a significant proliferative response. Additionally, intact anti-immunoglobulin but not its Fab fragments activated the B cells. An anti-Fab effectively converted the inactive Fab-bound B cells into producers of MNL CTX, suggesting that the basic mechanism of activation depended upon cross-linking of receptors. Thus, interaction of B-cell surface receptors such as Fc, Ig, and C3 sites with mitogenic as well as nonmitogenic molecules capable of bridging the receptors appears to trigger B-cell mediator production.
THE INTERACTION OF IgE WITH RAT BASOPHILIC LEUKEMIA CELLS
Authors: Kulczycki Anthony , Metzger Henry
Published: June 2004

Previous studies indicated that cultured rat basophilic leukemia cells have surface receptors which bind IgE with high specificity. In this paper we describe some quantitative aspects of the phenomenon. The reaction mechanism appears to consist of a simple reversible binding reaction with k1 = 9.6 x 104 M–1 sec–1 and k–1 ⩽ 1.6 x 10–5 sec–1 at 37°C. The calculated KA is therefore ⩾ 6 x 109 M–1. The activation energy of binding was found to be 7.8 kcal/mol. The number of binding sites/cell varied between 3 x 105 to over 1 x 106. The binding was insensitive to pH's between 6–8 but at pH 3.0 complete dissociation of bound IgE occurred in ∼ 1 min at 0°C leaving the receptors for IgE intact. Ca++ plus EDTA and Mg++ plus EDTA produce a fairly marked reduction in binding capacity though these reagents alone produce much smaller effects.
HOST-PARASITE INTERACTION IN THE RAT RENAL PELVIS
Authors: Silverblatt Fredric J.
Published: June 2004

The initial interaction between bacteria and the renal pelvic epithelium may determine whether intrarenal infection occurs. A model of retrograde pyelonephritis was employed to study these events by electron microscopy. Female rats received an intravesicular inoculation of a 0.5-ml suspension of Proteus mirabilis containing 108 organisms. At intervals after inoculation, the kidneys were fixed by intravascular perfusion and the tissues were prepared for electron microscopy.

During the first 24 h, increasing numbers of bacteria were seen to be attached by pili to the renal pelvic epithelial cells. The organism appeared to cross the mucosal barrier by several mechanisms: (a) penetration into the cytoplasm of intact epithelial cells, (b) passage between epithelial cells that were separated by excessive hydrostatic pressure generated during bladder inoculation, (c) passage across necrotic regions of the pelvis, and (d) translocation to the cortex by calicotubular backflow.

Whereas at inoculation bacteria possessed pili 40 Å in diameter (type III pili) 24 h after reflux, the predominant type of pili measured 70 A in thickness (type IV pili). Repetitive subculture induced a similar transition in vitro. To assess the influence of pili type on virulence in this model, 80 rats were challenged with either type III or type IV pilated organisms and the frequency of rats with cortical abscesses were compared at 1 wk. A significantly greater number of rats inoculated with type IV pilated Proteus manifested macroscopic evidence of infection. These results suggest that pili play a role in the pathogenesis of ascending pyelonephritis.
Macrophage-lymphocyte interaction. II. Antigen-mediated physical interactions between immune guinea pig lymph node lymphocytes and syngeneic macrophages.
Authors: Lipsky P E , Rosenthal A S
Published: June 2004

The effect of specific antigen on the development of physical interactions between lymph node lymphocytes (LNL) obtained from animals which had been immunized to that antigen and macrophages was examined. We found that the presence of antigen, either limited to the macrophage () or free in the medium, profoundly increased the degree of ) or free in the medium, profoundly increased the degree of Mphi-LNL interaction observed. This enhanced interaction was dependent on the coincidence in the cultures of Mphi bearing antigen and LNL from animals specifically immunized to that antigen. Although antigen-independent interactions developed equally well between syngeneic and allogeneic combinations of lymphocytes and macrophages, antigen mediated interactions required that macrophages and lymphocytes be syngeneic. Prolongation of antigen-mediated Mphi-LNL interactions resulted in the induction of LNL DNA synthesis, initially involving those lymphocytes physically associated with antigen-bearing Mphi. These studies are interpreted to indicate that physical interaction between immune lymphocytes and antigen-bearing Mphi represents a morphological correlate of the functional activation of immune lymphocytes. Further, it is suggested that the physical events involved in lymphocyte proliferation may proceed sequentially from antigen-independent reversible binding of lymphocytes by macrophages to prolonged antigen-stabilized interaction eventuating in the triggering of specifically immune lymphocytes.
The interaction in vitro between human polymorphonuclear leukocytes and Neisseria gonorrhoeae cultivated in the chick embryo.
Authors: Gibbs D L , Roberts R B
Published: June 2004

Cultivation of Neisseria gonorrhoeae in the allantoic cavity of 10-day chick embryos ensured the following necessary properties for subsequent quantitive in vitro phagocytosis studies of viable gonococci: log phase of growth, resistance to the cidal effect of fresh human serum, maintenance of colonial type, and absence of clumping. Employing a modification of the Maaloe technique, phagocytosis of log-phase type 1 and 2 gonococci by human PMN leukocytes did not occur in the presence or absence of serum. These findings indicate that log-phase type 1 and 2 gonococci possess antiphagocytic surface factors Stationary-phase organisms of the same colonial type were ingested and rapidly killed by human PMN leukocytes under similar experimental conditions, thus emphasizing the necessity to employ log-phase gonococci in the study of phagocytosis and antiphagocytic surface factors. Log-phase type 4 gonococci were ingested and rapidly killed by human PMN leukocytes in the presence of fresh human serum but not heat-inactivated serum or in the absence of serum. Morphologic studies demonstrated that log-phase viable gonococci attach to the surface membrane of human PMN leukocytes. Interiorization of avirulent but not virulent organisms was observed in the presence of fresh human serum. Gonococci-human PMN leukocyte interactions thus provide a model for the investigation of the nonimmunologic and immunologic parameters associated with the attachment and ingestion stages of phagocytosis.
Cell surface immunoglobulin. XI. The appearance of an IgD-like molecule on murine lymphoid cells during ontogeny.
Authors: Vitetta E S , Melcher U , McWilliams M , Lamm M E , Phillips-Quagliata J M , Uhr J W
Published: June 2004

An Ig molecule containing L chains and H chains similar to human delta-chains has been detected on the surface of radioiodinated murine lymphoid cells. Newborn mice have only IgM on their splenocytes. Between 10 and 15 days, the IgD-like molecule appears and increases in amount until 3 mo of age, when it is the predominant cell surface Ig in terms of radioactivity. IgD is found only in peripheral lymphoid tissues and is present in larger amounts on peripheral lymph node cells (approximately 85% of surface Ig) than on splenocytes (approximately 50%). IgD is also present in comparable amounts on cells from both nu/nu and germfree mice, indicating that its expression may be independent of both thymic influence and antigenic stimulation. These studies suggest that there is a switch from cell surface IgM to IgD that occurs during differentiation of virgin B lymphocytes in the spleen.
Fetuin, an inhibitor of lymphocyte transformation. The interaction of fetuin with phytomitogens and a possible role for fetuin in fetal development.
Authors: Yachnin S
Published: June 2004

Fetuin, the bovine alpha-fetoprotein, contains glycopeptide sequences similar to those found on red cells. As a result, it is capable of strong physical interaction with the phytohemagglutinin isomitogens (H-PHAP) which possess two or more R (red cell binding) subunits as part of their tetrameric structures. Fetuin shows little or no interaction with L-PHAP, a phytohemagglutinin made up of four L subunits which also lack red cell affinity. Despite these differences fetuin is able to inhibit both H- and L-PHAP-induced lymphocyte transformation and is also capable of inhibiting the mitogenic effects of pokeweed mitogen, concanavalin A, antithymocyte antiserum, and the one-way mixed lymphocyte culture. In the case of L-PHAP, the inhibitory effect of fetuin is proportional to the intensity of the mitogenic stimulus. The inhibitory effects of fetuin upon lymphocyte transformation may result from perturbation or "blindfolding" of the cell membrane in a manner analogous to other immunosuppressive serum alpha-globulins. Alpha-Fetoproteins may play an immunoregulatory role during fetal development.
Cell interactions between histoincompatible T and B lymphocytes. VII. Cooperative responses between lymphocytes are controlled by genes in the I region of the H-2 complex
Authors: Katz DH , Graves M , Dorf ME , Dimuzio H , Benacerraf B
Published: June 2004

The results of this study provide compelling evidence for the existence of the gene or genes controlling optimal T-B-cell cooperative interactions in the designated I region of the H-2 gene complex. Previously, we have speculated that the relevant gene(s) involved may well be located in this region based on several observations from our earlier work in this area (3, 5, 6). Thus, in the preceding paper, we showed that T and B cells from B10.BR and A strain mice developed effective cooperative interactions in vitro to DNP-KLH in a system identical to the one reported herein. Since these mice differ for genes in the S and D regions of H-2 but are identical for K and I region genes, we were able to localize the critical genes to the K-end of H-2.
Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level.
Authors: Gearhart P J , Sigal N H , Klinman N R
Published: June 2004

Immune responsiveness to phosphorylcholine (PC) in BALB/c mice has been characterized by combining (a) usuage of highly sensitive radioimmunoassays for quantitation of antibody, heavy-chain class, and idiotype on a weight basis; (b) isolation of PC-specific B cells in fragment cultures; and (c) stimulation in a carrier-primed environment with the PC hapten coupled to carrier through a tripeptide spacer in order to maximize carrier recognition. The specificity and accuracy of the radioimmunoassays have veen verified by specific inhibition, lack of nonspecific binding, and excellent concordance of values for monoclonal antibody concentration obtained independently for Fab and idiotype content. The latter evidence also serves as strong confirmation of the monoclonality of in vitro monofocal responses as well as the preservation of the idiotype on antibodies of differing immunoglobulin classes. The results indicate that while B cells expressing the TEPC 15 idiotype predominate, other idiotypes may be represented by 2-50% of PC-specific precursors, and monoclonal antibodies even of the TEPC 15 idiotype are produced in both the IgM and IgG1 immunoglobulin classes. These findings are confirmed by the analysis of serum antibodies produced in carrier-primed mice immunized with hapten coupled through a tripeptide spacer, thus re-emphasizint the enhancement of primary responsiveness, particularly IgG1 production, by maximizing carrier recognition. The finding of idiotype diversity in the PC response, as well as diversity of expression in terms of quantity and immunoglobulin class of antibody synthesized by the clonal progeny of B cells within the TEPC 15 clonotype, emphasize the heterogeneity of the B-cell population both in terms of specificity repertoire and the physiological state of cells even within a single clonotype.
Pili on meningococci from primary cultures of nasopharyngeal carriers and cerebrospinal fluid of patients with acute disease.
Authors: DeVoe I W , Gilchrist J E
Published: June 2004

The nasopharynx of known meningococcal carriers without signs of acute meningococcal disease as well as cerebrospinal fluid from patients with acute meningococcal disease were cultured on Thayer-Martin agar. Pili were observed in negatively stained preparations of over 80% cells from all primary cultures of both nasopharnyx and cerebrospinal fluids. Although pili were abundant on cells from all primary cultures, all pili were lost on serial subculture in the laboratory. This loss of pili from the cell surface on laboratory subculture was not accompanied by a concomitant loss of cell wall blebs.