bluuebunny/crossref_metadata_2025 huggingface dataset:
Requirement for persistent extracellular antigen in cultures of antigen-binding B lymphocytes.
Authors: Pike B L , Nossal G J
Published: June 2004

A system was established to assess the requirement for continuous presence of antigen in B-lymphocyte activation to antibody formation. Mouse spleen B lymphocytes, enriched for cells bearing anti-NIP (hapten 4-hydroxy-3-iodo-5-nitrophenylacetic acid) receptors, were pretreated briefly with NIP-POL (polymerized flagellin) antigen, washed, and added in small numbers to microcultures. The behaviour of these cells was compared with that of cells cultured in the continuous presence of antigen. Unfractionated spleen cells were studied under similar conditions. In contrast to unfractionated cells, enriched cells could not be triggered effectively by brief contact with antigen at any concentration tested. Fewer cells were activated, and clone size was smaller after brief contact with antigen than when antigen was present continuously. Furthermore, brief contact at high concentration did not cause tolerance induction.
Selective expression of H-2 (i-region) loci controlling determinants on helper and suppressor T lymphocytes.
Authors: Okumura K , Herzenberg L A , Murphy D B , McDevitt H O , Herzenberg L A
Published: June 2004

Data presented here show that locidentify in the I-region of the H-2 gene complex are selectively expressed in different functional T-cell subpopulations. These loci are closely linked (or possibly identical) to loci that control immune responses. They control surface determinants which identify helper and suppressor T lymphocytes. Determinants described here on allotype suppressor T cells (Ts) are found on normal (nonsuppressed) lymphoid cells, but are not found on helper T cells (Th). These determinants are controlled by a locus mapping in the I region of the H-2 complex. In an accompanying publication we show that this locus (Ia-4) marks a new I subregion (I-J) and is expressed only on T cells. Thus Ia-4 determinants idenfity a T-cell subpopulation which includes Ts but not Th. Th also carry identifying surface determinants controlled by loci that map to the H-2 complex, probably within the I region. These determinants are not found on Ts. Data presented also establish that loci in the I region control determinants on Th, but do not conclusively demonstrate that these are the determinants that distinguish Th from Ts. The selective expression of H-2-controlled determinants on Ts and Th suggests that these determinants are directly involved in immunoregulation.
A new I subregion (I-J) marked by a locus (Ia-4) controlling surface determinants on suppressor T lymphocytes.
Authors: Murphy D B , Herzenberg L A , Okumura K , Herzenberg L A , McDevitt H O
Published: June 2004

In an accompanying publication we show that a subpopulation of T lymphocytes, which includes allotype suppressor T cells, selectively expresses I-region determinants. In this report, we show that these determinants are controlled by a new locus, Ia-4. Unlike the classically defined Ia antigens, they are not found on B lymphocytes. Antibody against Ia-4 determinants cannot be detected by conventional dye exclusion cytoxicity assays, suggesting that they are present on a small subpopulation (less than 10%) of peripheral T lymphocytes. The Ia-4 locus marks a new I subregion, provisionally designated I-J. This chromosomal segment is defined by the crossover positions in strains B10.A(5R) (K-end boundary) and B10.HTT (D-end boundary), and maps between the I-B and I-C subregions.
Properties of the antigen-specific suppressive T-cell factor in the regulation of antibody response of the mouse. IV. Special subregion assignment of the gene(s) that codes for the suppressive T-cell factor in the H-2 histocompatibility complex.
Authors: Tada T , Taniguchi M , David C S
Published: June 2004

The locus of the gene that codes for the antigen-specific suppressive T-cell factor was determined to be in a new subregion "I-J" which locates between I-B and I-C subregions in the H-2 histocompatibility complex. This was shown by two different lines of evidence: (a) The absorbing capacity for the suppressive T-cell factor of several alloantisera against restricted I subregions did not correlate with their specificity for previously known Ia molecules which are coded for by genes in I-A and I-C subregions, but was associated with the specificity for the products of genes putatively present between I-B and I-C subregions. By the occurrence of special recombinant strains, i.e. B10.A(5R), B10.A(3R), B10.S(9R), and B10.HTT, which differ with respect to the I-J subregion, we were able to produce alloantisera which distinguish I-J subregion gene products. The absorption studies using these special alloantisera directed to I-J subregion clearly indicated that the suppressive T-cell factor is a product of I-J subregion gene(s), and that the molecule is distinct from known Ia molecules expressed on splenic B cells. (b) Taking advantage of the fact that there is a strict histocompatibility requirement for the effective suppression between the donor and recipient strains of the suppressive T-cell factor, we were able to determine the required identities of the genes in the H-2 complex existing among those present between I-B and I-C. Again, utilizing the T-cell factors obtained from special recombinant strains, i.e. B10.A(4R) and B10.A(5R), we were able to locate the gene that codes for the suppressive T-cell factor reactive only with relevant haplotype strains between I-B and I-C subregions. These results are most reasonably explained by the presence of a new subregion I-J which is specialized in coding for the suppressive T-cell factor as a different molecule from previously known Ia molecules.
The effect of allogeneic presensitization on H-Y graft survival and in vitro cell-mediated responses to H-y antigen.
Authors: Gordon R D , Mathieson B J , Samelson L E , Boyse E A , Simpson E
Published: June 2004

C57BL/6 and C57BL/10 female mice were grafted with skin from male or female donors incompatible for H-2 and/or non-H-2 antigens. Syngeneic male grafts applied after the rejection of primary allografts or syngeneic male grafts were rejected in accelerated (second set) fashion, whereas male grafts applied after primary female grafts were not. In addition, C57BL/10 female spleen cells, primed in vivo with an allogeneic (BALB/c, CBA, or B10.BR) male graft and challenged in vitro in mixed lymphocyte culture with syngeneic (C57BL/10) male cells, produced cytotoxic cells specific for syngeneic male target cells. We conclude that at least some component of H-Y is detected by female responder cells on allogeneic male cells, and that the second set cell mediated response to H-Y is not necessarily restricted by the H-2 haplotype of the primary sensitizing strain. Moreover, (CBA X B10) F1 females, primed in vivo with male cells of one parental haplotype (B10 or CBA) and challenged in vitro with male cells of the other parental haplotype (CBA or B10), fail to lyse male target cells of either parental haplotype. It therefore seems unlikely that a helper determinant shared between B10 and CBA is sufficient to explain the ability of CBA male cells to prime H-2-restricted T-cell cytotoxic responses by B10 females.
Secretion of Ia antigens by a subpopulation of T cells which are Ly-1+, Ly-2-, and Ia-.
Authors: McKenzie I F , Parish C R
Published: June 2004

It was found that Ia antignes are rapidly secreted by a subpopulation of splenic T lymphocytes which are nonadherent and which express the surface phenotype Ly-1+, Ly-2-, and Ia-. Secretion of the Ia antigens was a metabolically active process which was inhibited by sodium azide and by Pactamycin, an inhibitor of protein synthesis.
Antigen-induced co-capping of IgM and IgD-like receptors on murine B cells.
Authors: Goding J W , Layton J E
Published: June 2004

Double fluorescence studies indicated that most mature lymphocytes of 11-52-wk-old mice possess both IgM and IgD-like surface immunoglobulins, while spleen cells from neonatal mice possess surface IgM only. These molecules cap independently with class-specific antisera, but co-cap when capping is induced by antigen. It is proposed that the two heavy chains on individual lymphocytes possess similar or identical antigen-combining sites.
Histaminase release from human granulocytes.
Authors: Zeiger R S , Twarog F J , Colten H R
Published: June 2004

Histaminase (EC-1.4.3.6), one of the two catabolic enzymes for histamine, is contained in human granulocytes. Opsonized zymosan or the calcium ionophore A-23187 induce a dose-dependent release of histaminase from human granulocytes in vitro. Release is completed within 30 min, is temperature dependent, and requires divalent cations. Opsonized zymosan-induced histaminase release was maximal in the presence of both calcium and magnesium, whereas ionophore release was magnesium independent. The total cellular content of histaminase could be released by both opsonized zymosan and ionophore. In contrast, only 25% of the cellular beta glucuronidase, a lysosomal enzyme, was released after maximal stimulation with opsonized zymosan; there was minimal release of beta glucuronidase with ionophore. Zymosan- and ionophore-induced histaminase release was inhibited by agents that are presumed to interfere with cell metabolism and disrupt microtubules. Human granulocytes therefore may modulate the effect of histamine by releasing histaminase at a site of inflammation. Studies of granulocyte histaminase release in vitro may also provide a new model to explore granulocyte function and secretion.
Alternative pathway of complement: recruitment of precursor properdin by the labile C3/C5 convertase and the potentiation of the pathway.
Authors: Medicus R G , Götze O , Müller-Eberhard H J
Published: June 2004

In this study the physiological role of properdin and the differential subunit composition of the solid phase enzymes of the pathway have been explored. Cell-bound C3 and C5 convertase differ in their C3b requirement. Apparently one molecule of C3b is sufficient to allow formation of C3 convertase (C3b,B), whereas two or more are required for generation of C5 convertase (C3bn,B). This conclusion was drawn from results indicating the critical role of the spacial distribution of C3b molecules on the cell surface in enzyme formation. While the C3/C5 convertase is fully capable of acting on C5 and thereby initiating the assembly of the cytolytic membrane attack complex, it is exceedingly labile and vulnerable to destruction by the C3b inactivator. It is the apparent role of properdin to confer a degree of stability upon the labile enzyme and to protect its C3 convertase function against enzymatic destruction. To achieve these effects, precursor properdin (pre-P) is recruited in a binding-activation reaction by the labile C3/C5 convertase. Multiple C3b molecules appear to be needed for the formation of properdin-activating principle. Three modes of regulation have been described, which involve spontaneous dissociation enzymatic degradation by C3b inactivator and disassembly by beta1H. The functional differences of pre-P and activated properdin (P) were delineated, pre-P displaying a weak affinity for C3b and P the capacity of strong interaction, P generating a soluble C3 convertase in serum and pre-P being unable to do so. Because of the profound differences between native pre-P and the laboratory product P, the question was raised as to whether soluble P represents an unphysiological form of the protein. On the basis of this and other studies, the conclusion was reached that in vitro properdin recruitment constitutes the terminal event of the properdin pathway, and that properdin augments the function of C3/C5 convertase without changing its substrate specificity.
Independent differentiative pathways of Ly1 and Ly23 subclasses of T cells. Experimental production of mice deprived of selected T-cell subclasses.
Authors: Huber B , Cantor H , Shen F W , Boyse E A
Published: June 2004

When B mice are supplied with Ly1 or Ly23 cells they acquire, over the next 6 mo, only the immune functions associated with each of these T-cell subclasses, respectively. The T-cell population of these "B-Ly1" and "B-Ly23" mice mice also remains restricted to the Ly1 and Ly23 subclass phenotypes. Thus the Ly1 and Ly23 populations are derived from two separate lines of differentiation and are not sequential stages of a single differentiative pathway.
Effects of anti-Ia sera on mitogenic responses. III. Mapping the genes controlling the expression of Ia determinants on concanavalin A-reactive cells to the I-J subregion of the H-2 gene complex.
Authors: Frelinger J A , Niederhuber J E , Shreffler D C
Published: June 2004

We have shown that the Ia determinants expressed on nylon wool-purified T lymphocytes reactive to concanavalin A (Con A) in serum-free media are coded in a single I subregion of the H-2 gene complex. This region, I-J, is defined by two pairs of intra-H-2 recombinant haplotypes: H-2t3, H-2t4 and H-2i3, H-2i5, carried by B10.HTT, B10.S(9R), B10.A(3R), AND B10.A(5R), respectively. No activity against Con A-reactive T cells has been detected in any antiserum that was produced in strain combinations which shared a common I-J region. This suggests that Ia antigens expressed on Con A-reactive T cells are restricted to the I-J subregion.
Control of B-lymphocyte function. I. Inactivation of mitogenesis by interactions with surface immunoglobulin and Fc-receptor molecules.
Authors: Sidman C L , Unanue E R
Published: June 2004

Mouse spleen cells were incubated with anti-Ig antibodies for 1 h, washed, exposed to LPS for 1 h, washed, and their DNA synthetic responses assayed 2 days later. It was shown that the 1-h incubation with anti-Ig antibodies produced a profound, internal, and long lasting state of inactivation in the B cells. Experiments with anti-Ig fragments and other ligands showed that the inactivation occurred optimally when both surface Ig molecules and Fc receptors were bound simultaneously. The role of the classical capping and clearing cycle was also investigated. It was shown that capping and clearing were neither necessary nor sufficient for the inactivation to occur, and that the signals, but only secondarily the ligands themselves, were transmitted across the membrane. Capping and clearing were viewed as a natural regulatory mechanism by which the B cell attempts to clear its membrane of perturbations and signals from the exterior.
Serological detection of variable region (Vh) subgroups of Ig heavy chains.
Authors: Forre O , Natvig J B , Kunkel H G
Published: June 2004

Serological test systems were established for determining the heavy-chain variable region (Vh) subgroups of immunoglobulin heavy chains. Myeloma proteins with known Vh subgroups based on amino acid sequence were utilized as the primary basis of reference for analysis by hemagglutination and hemagglutination inhibition. Good agreement between the chemical and serological typing was obtained and nonoverlapping systems established for the three major Vh subgroups. In a survey of 167 myeloma proteins, all except two were exclusively positive in one of the three systems. The two exceptions may represent a fourth subgroup. There was an overall incidence ratio of 1:2:3 for VhI:VhII:VhIII subgroups. Some differences in the overall ratios were encountered within the immunoglobulin classes. Certain advantages of the serological typing antisera were discussed with special emphasis on their use for studies of Vh antigens on the membranes of lymphocytes.
Suppression by autogenous complementary idiotypes: the priority of the first response.
Authors: Rowley D A , Köhler H , Schreiber H , Kaye S T , Lorbach I
Published: June 2004

Complementary idiotypes or antibodies are considered to have combining site structures which are at least partly directed against each other. Complementary antibodies were induced in A/He mice by immunization with phosphorylcholine (PC)-containing antigens and by immunization with the PC-binding IgA myeloma protein TEPC-15 (T15). Both responses were monitored by enumerating plaque-forming cells (PFC) and assaying serum antibody levels against the corresponding antigens. Mice immunized at least three times with T15 in adjuvants had markedly suppressed responses to subsequent immunization with PC; similarly, mice preimmunized multiple times with PC had suppressed responses to immunizations with T15. In contrast, mice immunized with T15 in the interval between "primary" and "secondary" immunizations with PC had undiminished PFC responses to both antigens but significantly decreased antibody titers to PC. Simultaneous responses were also induced by immunizations with T15 superimposed on weekly immunizations with PC; with this regime, immunization with T15 actually enhanced the PFC response to PC, but serum antibody to PC was significantly lower than for mice immunized with PC only. Levels of serum antibody to PC were probably lower, either because anti-PC antibody was complexed with the complementary antibody directed against T15, or because the antibody directed against T15 prevented synthesis and/or release of anti-PC antibody by cells in vivo. Thus, an established prior autogenous immune response can dramatically suppress a subsequent primary complementary response, but the effects of complementary responses on each other are more complex with different sequences of immunization. Also, the effects of variables such as the amounts and ratios of the classes of antibodies on regulation of complementary responses remain to be defined.
Role of B lymphocytes in cell-mediated immunity. I. Requirement for T cells or T-cell products for antigen-induced B-cell activation.
Authors: Wahl S M , Rosenstreich D L
Published: June 2004

Although B lymphocytes can be triggered by B-cell mitogens and by certain other molecules to produce lymphokines, they do not produce lymphokines when stimulated with specific soluble protein antigens. We have investigated whether T-cell help would enable B cells to produce lymphokines when activated by antigens. Addition of small numbers of T cells to B-cell cultures resulted in significant production of a monocyte chemotactic factor. T cells could be replaced by supernates of antigen-stimulated T cells, demonstrating both that the chemotactic factor was B-cell-dervied and that T-cell help was mediated by a soluble factor. Although the T-cell factor was nonantigen specific, B-cell activation required the presence of both antigen and T-cell factor. Thus, it appears that although dependent upon T cells, B lymphocytes may play an important role in amplification of cell-mediated immune responses.
Regulatory mechanisms in cell-mediated immune responses. IV. Expression of a receptor for mixed lymphocyte reaction suppressor factor on activated T lymphocytes.
Authors: Rich S S , Rich R R
Published: June 2004

Suppression of the mixed lymphocyte reaction (MLR) by a soluble factor produced by alloantigen-activated spleen cells requires genetic homology between the factor-producing cells and responder cells in MLR. The ability of lymphocytes used as MLR responder cells to adsorb MLR suppressor factor was tested to investigate the expression of a receptor structure for suppressor molecules. Normal spleen or thymus cells had no effect on suppressor activity. Concanavalin A (Con A)-activated thymocytes, however, effectively removed suppressor activity, suggesting that the receptor is expressed only after activation and is not present or not functional on resting cells. Significantly neither phytohemagglutinin- nor lipopolysaccharide-activated lymphoid cells absorbed the factor. Furthermore, only Con A-activated thymocytes demonstrating genetic homology with the cell producing suppressor factor for H-2 regions to the right of I-E were effective absorbants. Alloantigen-stimulated spleen cells syngeneic to the suppressor cell also removed suppressor activity. These data support an hypothesis that subsequent to stimulation in MLR, T lymphocytes express a receptor, either through synthesis or alteration of an existing molecular structure, which then provides the appropriate site for interaction with suppressor molecules.
Antibody-mediated suppression of grafted lymphoma. IV. Influence of time of tumor residency in vivo and tumor size upon the effectiveness of suppression by syngeneic antibody.
Authors: Shin H S , Economou J S , Pasternack G R , Johnson R J , Hayden M L
Published: June 2004

In the suppression of the growth of a mouse lymphoma 6C3HED by antibody, the effectiveness of antibody in suppressing growing or established tumor cells and comparable number of freshly injected tumor cells is quantitatively similar. The effectiveness of antibody diminishes markedly when the number of tumor cells per mouse reaches the level of 10(6) due to the development of a macrophage shortage. At the 10(5) tumor cells level, antibody-mediated suppression takes place in an optimal manner and between 10(5) and 10(4) tumor cell numbers, the amount of antibody required to suppress 50% of the tumor cells is directly proportional to the number of tumor cells suppressed.
Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection.
Authors: Gresser I , Tovey M G , Bandu M E , Maury C , Brouty-Boyé D
Published: June 2004

The role of interferon in the pathogenesis of encephalomyocarditis (EMC) virus infection was determined by treating mice with potent, partially purified sheep anti-mouse interferon globulin. In control mice, EMC virus was present in low titers in various visceral organs but attained high titers in the brain towards the 4th to 5th day, at which time mice died with signs of central nervous system disease. In mice treated with anti-mouse interferon globulin, virus was present in high titer in visceral organs 24--36 h after viral inoculation and virtually all mice were dead by 45 h. This rapid evolution of EMC virus infection was not observed in mice treated with the globulin fraction prepared from a normal sheep, from a sheep exhibiting a low anti-mouse interferon-neutralizing titer, nor from a sheep having a high titer of antibody to human leukocyte interferon. The experimental results indicated that anti-interferon globulin neutralized the interferon liberated by virus-infected cells, thus permitting extensive virus multiplication in several visceral organs. We conclude that interferon is an important early component of host resistance to this virus infection.
Control of mating preferences in mice by genes in the major histocompatibility complex.
Authors: Yamazaki K , Boyse E A , Miké V , Thaler H T , Mathieson B J , Abbott J , Boyse J , Zayas Z A , Thomas L
Published: June 2004

When a male mouse is presented with two H-2 congenic two female in estrus, his choice of a mate is influenced by their H-2 types. The term "strain preference" is used to describe the general tendency of the male population of one inbred strain to prefer two female of one H-2 type rather than another. The term "consistency of choice" is used to describe the added tendency of particular two males of one inbred strain, in sequential mating trials, to prefer two females of the H-2 type they chose in previous trials. Statistical analysis showed trends in the data that support the following conclusions: (a) The choice is made by the male, not the female. (b) The strain preference of two males may favor two females of dissimilar H-2 type (four of six comparisons), or of similar H-2 type (one of six comparisons). (c) Consistency of choice does not always correspond with strain preference. In one of six comparisons of H-2 genotypes there was no strain preference but pronounced consistency of choice by individual two male.This suggests memory, but fortuitous bias is not excluded. (d) Strain preference of the same male population may favor two male of the same or a different H-2 type, depending on which different H-2 type is offered as the choice alternative to self.These findings conform to a provisional model in which olfactory mating preference is governed by two linked genes in the region of H-2, one for the female signal and one for the male receptor. These mating preferences could in natural populations serve the purpose of increasing the representation of particular H-2 haplotypes or of maintaining heterozygosity of genes in the region of H-2.
Role of self-carriers in the immune response and tolerance. I. B-cell unresponsiveness and cytotoxic T-cell immunity induced by haptenated syngeneic lymphoid cells.
Authors: Scott D W , Long C A
Published: June 2004

Normal spleen cells cultured with TNP-modified syngeneic spleen cells fail to mount an anti-TNP PFC response to TNP-ficoll or TNP-red blood cells,but go on to generate cytotoxic T cells directed at hapten-modified H-2.These results suggest that hapten-modifeid spleen cells may differentially induce B-cell tolerance and T- (Ly 2,3) cell immunity. The differential response to modified self by lymphocyte subpopulations is discussed.
Fractionation of human T lymphocytes on wheat germ agglutinin-sepharose.
Authors: Hellström U , Dillner M L , Hammarström S , Perlmann P
Published: June 2004

T cells from human peripheral blood was purified by fractionation on columns charged with human immunoglobulin and rabbit anti-human immuno-globulin. When assayed with 125I- or fluorescein isothiocyanate-labeled wheat-germ agglutinin (WGA), a weakly binding and a strongly binding subpopulation could be distinguished. These T-cell subpopulations were fractionated on columns charged with WGA, convalently bound to Sepharose 6MB. The cells responding to the mitogens leukoagglutinin from Phaseolus vulgaris and concanavalin A were enriched in the strongly binding subpopulation (approximately 20% of the T cells) while they were depleted from the weakly binding subpopulation.
Structural determinants of the eosinophil: chemotactic activity of the acidic tetrapeptides of eosinophil chemotactic factor of anaphylaxis.
Authors: Goetzl E J , Austen K F
Published: June 2004

The acidic tetrapeptides of ECF-A, Ala/Val-Gly-Ser-Glu, exhibit peak in vitro chemotactic activity for human eosinophils at concentrations of 3 X 10(-8) M to 10(-6) M, and rapidly deactivate eosinophils to homologous and other stimuli at concentrations as low as 10(-10) M. The analogue Leu-Gly-Ser-Glu reaches peak activity at 10(-8)M-10(-7)M, while Phe-Gly-Ser-Glu requires 10(-4)M to elicit a peak response. Although inversion of the order of glycine and serine does not alter the eosinophil chemotactic activity of the tetrapeptides, deletion of glycine increases by 10-fold the concentration required for peak chemotactic activity, indicating the critical nature of the spacing between NH2- and COOH-terminal residues. The substituent COOH-terminal tripeptide, which is only marginally chemotactic, irreversibly suppresses eosinophil chemotactic responsiveness at a concentration 10,000-fold higher than concentrations necessary for deactivation by the intact tetrapeptide. The high concentration of tripeptide required for this cell directed effect, which is assumed to be analogous to deactivation, is attributed to the absence of the NH2-terminal residue which would facilitate effective interaction with the eosinophil. A substituent NH2-terminal tripeptide and amides of the NH2-terminal amino acids, which are devoid of chemotactic and deactivating activities, reversibly inhibit the tetrapeptide stimulus in a dose-response fashion. The additional finding that the NH2-terminal tripeptide protects the eosinophil from deactivation by the intact tetrapeptide confirms that the competitive interaction is stimulus specific.
Evidence for the catabolism of polychlorinated biphenyl-induced cytochrome P-448 by microsomal heme oxygenase, and the inhibition of delta-aminolevulinate dehydratase by polychlorinated biphenyls.
Authors: Maines M D
Published: June 2004

Polychlorinated biphenyls (PCB) are potent inducers of hepatic microsomal CO-binding hemoprotein P-448 (P1-450) and of delta-aminolevulinate synthetase (ALAS) activity. Inorganic cobalt was able to block PCB induction of cytochrome P-448 and to modify the PCB effect on ALAS activity in a time-dependent manner. PCB were also found to decrease the activity of delta-aminolevulinic acid dehydratase (ALAD) in liver. Pretreatment of rats with cobalt (30 min) produced the following changes in PCB actions on heme metabolism in liver: (a) augmentation of the porphyrinogenic effect of PCB, as determined by the total porphyrin content and ALAS activity; (b) augmentation of PCB inhibition of ALAD activity; and (c) blockade of induction of microsomal hemoprotein (cytochrome P-448). PCB did not interfere with cobalt induction of hepatic heme oxygenase activity. The sequence of administration of the metal and the PCB was important in relation to the changes produced in hepatic ALAS activity and microsomal hemoprotein and heme contents. When cobalt was administered 24 h after PCB treatment, the magnitude of induction of ALAS by PCB was lowered, and there was a great reduction in microsomal hemoprotein and heme contents. The renal response to PCB was different than that of the liver. In the kidney, PCB blocked the induction of heme oxygenase and depletion of cellular heme produced by cobalt. Furthermore, renal microsomal heme content was increased by PCB treatment alone or in combination with cobalt. It is concluded that (a) the heme moiety of microsomal cytochrome P-448 is metabolized by the heme oxygenase system, and it is suggested that for this catabolism to take place, the hemoprotein must be first converted to the denatured form of the hemoprotein, cytochrome P-420; (b) that the synthesis of heme in the kidney and the liver are regulated through different mechanisms; and (c) that ionic cobalt controls activity of ALAS by first inhibiting synthesis of the enzyme followed by the indirect induction of the enzyme as a result of the catabolism of heme, the physiological repressor of ALAS, by the metal-induced heme oxygenase. Thus microsomal heme oxygenase may be viewed as having an overall regulatory role in relation to mictochondrial ALAS by virtue of its ability to catabolize endogenous heme.
The induction of macrophage spreading: role of coagulation factors and the complement system.
Authors: Bianco C , Eden A , Cohn Z A
Published: June 2004

Unstimulated mouse peritoneal macrophages, attached to either glass or plastic substrates, responded to factors generated in serum and plasma by spreading and increasing their apparent surface area up to eightfold. Two distinct and dissociable systems were involved. The first appears related to the distinct and dissociable systems were involved. The first appears related to the contact phase of blood coagulation. It is activated by glass and not plastic surfaces, depleted by kaolin adsorption, and inhibited by soybean trypsin inhibitor. In contrast, a separate complement-dependent system can be generated in kaolin-adsorbed plasma. Activation of the complement system can occur either by the alternate or classical pathways and generates a relatively small effector molecule which is dialyzable. These factors presumably influencing the surface membrane and underlying structures may explain the rapid spreading of activated macrophages observed after both infections and chemical peritoneal inflammatory agents.
Specific binding of K- and I-region products of the H-2 complex to activated thymus-derived (T) cells belonging to different Ly subclasses.
Authors: Nagy Z , Elliott B E , Nabholz M
Published: June 2004

Responder cells [C57BL/6J X A.TL)F1 lymph node cells depleted of bursa equivalent-derived (B) cells by filtration through nylon wool columns] were activated against incompatible K-region and I-region products together under conditions where these antigens are presented on separate stimulator cells. The resulting T blasts were stained with different concentrations of antisera directed against incompatible stimulator K-region or I-region products, or both. We obtained results that strongly suggest that in these cultures each activated responder blast stains with antiserum directed against either K-region or I-region products, but not both. Responder blasts from the same cultures were treated with antiserum and complement (C) directed against either Ly-1.2 or Ly-2.2 T-cell-specific surface antigens. Anti-Ly-1.2 serum and C specifically eliminates virtually all responder blasts staining with antiserum directed against stimulator I-region products; whereas anti-Ly-2.2 serum reduces to background levels the proportion of cells staining with antiserum against stimulator K-region products. The results obtained suggest that T cells binding stimulator K-region and I-region products, respectively, belong to two different subclasses distinguishable by their Ly phenotypes. Possible explanations for this association of T- cell subclass and specificity are discussed.
The requirement of an adherent cell substratum for the growth of developing plasmacytoma cells in vivo.
Authors: Cancro M , Potter M
Published: June 2004

The intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) produces an environment conductive to primary plasmacytoma growth in as few as 3 days. After pristane injection, the total free peritoneal cell population increases from a normal value of 1.55 X 10(6) to 5.28 X 10(6) and remains at this elevated level for at least 50 days. The adherent peritoneal cell population, composed of both mononuclear cells and polymorphonuclear leukocytes, is the primary source of this increase. In the pristane-conditioned peritoneum, these cells rapidly form a chronic granuloma on the peritoneal connective tissues. Daily subcutaneous treatment of mice with 0.5 mg of hydrocortisone beginning simultaneously with pristane injection prevents the increase in the peritoneal cell population, granuloma formation, d the production of a conditoned environment. In mice treated with hydrocortisone beginning 3 days after pristane injection, however, neither the peritoneal cell increase nor the production of a conditioned environment is prevented. The intraperitoneal injection of thioglycolate medium at 4-day intervals produces an elevation of the free adherent peritoneal cell population similar to pristane, but does not produce a granuloma or a conditioned environment. The intraperitoneal transfer of thioglycolate-induced adherent peritonel cells to mice treated with pristane and hydrocortisone simultaneously restores the production of a conditioned environment. These findings indicate that the adherent peritoneal cell population is responsible for the conditioning effect, and that the establishment of a resident population of these cells is necessary to produce conditioning.
The binding of human lactoferrin to mouse peritoneal cells.
Authors: Van Snick J L , Masson P L
Published: June 2004

Human iron-saturated Lf (FeLf), which was labeled with 125I or 50Fe, was found to combine with the membrane of mouse peritoneal cells (MPC) which consisted of 70% macrophages. The following experimental data suggested the involvement of a specific receptor. (a) The binding of FeLf to MPC reached a saturation point. (b) The binding of radioactive FeLf was inhibited by preincubating the cells with cold FeLf but not with human Tf, human aggregated and nonaggregated IgG, or beef heart cytochrome c (c) Succinylation and carbamylation of FeLf resulted in a loss of its inhibiting activity on the binding of radioactive FeLf. Removal of neuraminic acid from FeLf increased its inhibitory activity. (d) The ability of apoLf to inhibit the binding of FeLf to MPC was significantly lower than that of FeLf. The existence of a Lf receptor capable of concentrating Lf released from neutrophils on the membrane of macrophages could explain the apparent blockade of the release of iron from the reticuloendothelial system, which accounts for the hyposideremia of inflammation. A receptor for FeLf was also found on mouse peritoneal lymphocytes. The affinity constant of FeLf for both lymphocytes and macrophages was 0.9 X 12(6) liter/mol. Howerver, macrophages bound three times more FeLf molecules (20 X 10(6)) per cell than did lymphocytes (7 X 10(6)).
The specificity of cellular immune responses in guinea pigs. III. The precision of antigen recognition by T lymphocytes.
Authors: Janeway C A , Paul W E
Published: June 2004

T lymphocytes from guinea pigs immunized with 2,4-dinitrophenyl (DNP) derivatives of mycobacteria respond to a variety of DNP conjugates. Preincubation of such cells with a given DNP conjugate under conditions which lead to the inactivation of responding cells causes a loss of the response to that conjugate, but has little effect on the response to DNP coupled to unrelated carriers. Thus, the responses of such cells to a variety of DNP conjugates can best be explained by the presence of a mixture of highly specific cells each responding to a different antigenic dterminant rather than by the presence of T cells with specificity limited to the hapten itself. Furthermore, the activity of T cells from DNP-mycobacteria-primed donors could not be blocked by a variety of nonstimulatory DNP conjugates. This suggests that while such T cells clearly recognize DNP with great precision, the receptor does not contain a very high affinity site for the hapten. A possible model for such a T-cell receptor is discussed.
Cooperation across the histocompatibility barrier: H2d T cells primed to antigen in an H-2d environment can cooperate with H-2k B cells.
Authors: Waldmann H , Pope H , Munro A J
Published: June 2004

H-2d spleen cells derived from either tetraparental or semiallogeneic radiation bone marrow chimeras can be primed to antigen within H-2d recipients to generate helper T cells capable of cooperating in a secondary response with equal efficiency with H-2d or H-2k B cells. Thus it would seem that the cooperative act between T and B cells does not require that the T cell interacts with its target B cells by either cell interaction genes or via an altered self mechanism involving both antigen and the target B-cell I-region products. This does not preclude a requirement for associative recognition or altered self in the interaction of helper T cells with accessory cells.
Identification of a cell-surface antigen selectively expressed on the natural killer cell.
Authors: Glimcher L , Shen F W , Cantor H
Published: June 2004

We have studied the cell-surface phenotype of natural killer (NK) cells of NZB and B6 mice which react to an MuLV+ lymphoid tumor. (a) NK cells do not express Thy1, Ly2, or Ig surface markers. (b) NK cells express an antigen recognized by C3H anti-CE antiserum ('anti-Ly1.2 antiserum'). Inasmuch as NK activity of spleen cells from B6 and B6/Ly1.1 congenic strains were both equally sensitive to C3H anti-CE antiserum, the NK antigen is distinct from Ly1.2. This point was confirmed by the observation that alphaNK activity was removed by absorption of C3H anti-CE antiserum with spleen cells from either B6 or B6/Ly1.1 congenic strains. Absorption of C3H alphaCE serum with BALB/c thymocytes and spleen cells (which are Ly1.2+NK-) removed anti-Ly1.2 activity and left anti-NK activity intact. This absorption step could be circumvented by inserting the BALB/c genotype into the recipient immunized to CE cells (i.e., (C3H X BALB/c)F1 alphaCE spleen cells). This antiserum, provisionally termed 'anti-NK', defines a new subclass of lymphocytes which may play a central role in the immunosurveillance against tumors.
Isolation of variants in phagocytosis of a macrophage-like continuous cell line.
Authors: Muschel R J , Rosen N , Bloom B R
Published: June 2004

We have isolated cloned variants in phagocytosis from a cloned continuous murine macrophage-like cell line, J 774.2. A selection procedure against Fc receptor-mediated phagocytosis was devised using IgG-coated SRBC containing a toxic drug, tubercidin, as the lethal agent. A series of variant clones deficient in Fc receptor-mediated phagocytosis were isolated. Such variants occurred at low frequency (approximately 6 X 10(-5)), were stable, and appeared to possess Fc receptors. The degree to which they were defective in phagocytosis of IgG-coated SRBC varied from clone to clone, yet all clones, were able to phagocytize latex particles. The phagocytic defect in some variants could be corrected by the addition of 8 Br-cAMP, in others, the drug was without effect. It is likely, therefore, that different variants are defective in several distinct steps critical to Fc receptor-mediated phagocytosis.
Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus system: differential activity of IgG and IgM with different subpopulations of lymphocytes.
Authors: Lamon E W , Shaw M W , Goodson S , Lidin B , Walia A S , Fuson E W
Published: June 2004

Antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus (MSV) system was evaluated in terms of the differential ability of IgG and IgM from MSV regressor animals to induce cytotoxicity by lymphocytes from lymph node, spleen, and thymus. The cell-mediated cytotoxicity induced by both IgM and IgG was specific for target possessing the appropriate virally determined cell surface antigen(s). IgM induced cytotoxicity by lymphocytes from all the organs tested. However, differences in magnitude and efficiency were revealed. Lymph node cells and thymocytes were most efficient against IgM-coated target cells. Against IgG-sensitized target cells, spleen and lymph node cells were about equally active, but thymocytes were inactive. Cortisone treatment of the donors of effector cells revealed that the cortisone resistant subpopulation of thymocytes, 2 days after cortisone injection, exhibited an increased cytotoxicity against target cells treated with unfractionated antiserum and its IgM fraction. This subpopulation of thymocytes was also cytotoxic against IgG-coated target cells. At 12 days after cortisone injection, the repopulated thymus showed little change in activity, compared to control thymus, against antibody-coated target cells.
T-lymphocyte-enriched murine peritoneal exudate cells. IV. Genetic control of cross-stimulation at the T-cell level.
Authors: Schwartz R H , Horton C L , Paul W E
Published: June 2004

Antibodies raised against many structurally related antigens have been shown to cross-react extensively. Manifestations of T-cell immunity, on the other hand, appear to be more restricted in their ability to be elicited by cross-reacting antigens, although examples have been reported. This paper explores the nature of the cross-reactions at the T-cell level among the branched-chain copolymers (T,G)-A--L, (phi,G)-A--L, (H,G)-A--L, and G-A--L, as well as a related linear terpolymer, GAT, in a variety of mouse strains using the peritoneal exudate T-lymphocyte-enriched cells (PETLES) proliferation assay. (T,G)-A--L, (phi,G)-A--L, and GAT could cross-stimulate cells immune to the other two antigens, whereas (H,G)-A--L, (T,G)-Pro--L, and G-A--L showed no cross-stimulations. The extent of the cross-reactions varied with the mouse strain and was shown to be under the control of immune response genes. It was necessary for the strain to be able to respond to both the immunogen and the cross-reacting antigen, when used as an immunogen, in order for cross-stimulation to occur; however, this was not always sufficient. Several examples of unequal or one-way cross-reactions were found. In addition, the immune responses to (H,G)-A--L and (phi,G)-A--L showed no cross-reactions with the other antigen even though their Ir genes were both mapped to the K region or I-A subregion. The problem of accounting for such fine specificity of T-cell recognition in lieu of the genetic evidence demonstrating only Ir gene control of the response is discussed.
Immunochemical evidence for an additional H-2 region closely linked to H-2D.
Authors: Hansen T H , Cullen S E , Sachs D H
Published: June 2004

Anti-H-2 reagents have been tested on solubilized spleen cell preparations in combinations expected to be specific for D region products. Two different types of molecules were detected. One showed the expected reactivity with both antisera to private and antisera to public specificities. However, an additional molecule was detected which reacted only with antisera to public specificities. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis migration patterns indicated that both products have a similar molecular size of approximately 45,000 daltons. The data therefore present chemical evidence for the existence of a third H-2-associated gene product of 45,000 mol wt in addition to the classical H-2K and H-2D antigens.
Isolation by cell-column chromatography of immunoglobulins specific for cell surface carbohydrates.
Authors: Sela B A , Edelman G M
Published: June 2004

A new method of affinity chromatography using glutaraldehyde-fixed cells immobilized on Sephadex beads has been used to isolate immunoglobulins (Ig's) specific for cell surface glycoproteins. Ig's that specifically bound and agglutinated the same cells as those originally fixed on the columns were isolated from nonimmune sera of various species. Periodate treatment of the cell-columns and the free cells destroyed their ability to bind the Ig's, and the binding of the Ig's to untreated cells was inhibited by monosaccharides such as D-galactose and sialic acid. The binding of antibodies directed against cell surfaces obtained by immunizing animals with the same mouse tumor cell lines used on the columns (P388 and EL4) was not inhibited by various saccharides. Surface glycoproteins obtained from the mouse tumor cells by immunoprecipitation with the column-isolated Ig's yielded specific electrophoretic patterns that differed from those obtained using Ig's from the sera of rabbits immunized with the tumor cells. The data suggest that the Ig's isolated by cell-column chromatography were directed against carbohydrates, probably those in terminal positions of the polysaccharide portions of the tumor cell surface glycoproteins. Column-isolated Ig's specific for carbohydrates were also useful in studies of cell interactions in nonmammalian systems including Dictyostelium discoideum and Saccharomyces cerevisiae. The cell-column method appears to be adaptable to the isolation of a variety of molecules in addition to antibodies.
Thymus-like activities of sulphur derivatives on T-cell differentiation.
Authors: Renoux G , Renoux M
Published: June 2004

Levamisole and sodium diethyldithiocarbamate can induce in vivo thymocyte differentiation from precursor spleen cells of nu/nu mice and evoke indirect plaque-forming cells in nude mice immunized with sheep red cells. These sulphur drugs induce in thymusless mice the production of a serum factor which transfer in vivo immune enhancement and in vitro thymocyte differentiation. In vivo treatment with sulphur derivative can substitute for an alleged thymice hormone.