bluuebunny/crossref_metadata_2025 huggingface dataset:
ANTIBODY RESPONSE OF INBRED MOUSE STRAINS TO ORDERED TETRAPEPTIDES OF TYROSINE AND GLUTAMIC ACID ATTACHED TO MULTICHAIN POLYALANINE OR POLYPROLINE
Authors: Mozes Edna , Schwartz Michal , Sela Michael
Published: June 2004

Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.
EARLY AND DISCRETE CHANGES IN PERMEABILITY OF ESCHERICHIA COLI AND CERTAIN OTHER GRAM-NEGATIVE BACTERIA DURING KILLING BY GRANULOCYTES
Authors: Beckerdite Susan , Mooney Carolyn , Weiss J. , Franson R. , Elsbach Peter
Published: June 2004

Rapid killing of Escherichia coli by intact or disrupted rabbit granulocytes or by granulocyte fractions was found to be accompanied by an equally rapid increase in permeability of the E.coli envelope. This increase in permeability was detected by determining entry of substances that normally do not cross E.coli's permeability barrier, namely actinomycin D and o-nitrophenyl-ß-D-galactopyranoside (ONPG), a substrate for cytoplasmic ß-galactosidase.

Because E.coli continue to incorporate radioactively labeled precursors into bacterial RNA and protein for at least 1 h, despite rapid killing by granulocytes, entry of actinomycin D could be measured by its inhibitory effect on macromolecular synthesis. Entry was evident within minutes after exposure to granulocytes or granulocyte fractions and is independent of pH over a range of 6.5–9.0.

The effect of disrupted granulocytes or partially purified fractions on susceptibility of E.coli to actinomycin D and entry of ONPG is dose dependent. That the entry of actinomycin D and ONPG was not caused by gross destruction of the envelope is indicated by two sets of observations: (a) net influx of 42K was maintained for at least 15 min, even though efflux of potassium was immediately accelerated upon addition of bactericidal concentrations of granulocyte fractions; (b) ß-galactosidase did not leak out of E.coli under conditions that produce maximal inhibition by actinomycin D.

Different species of gram-negative bacteria exhibited different susceptibilities to the bactericidal and permeability effects of granulocyte fractions. Thus, three strains of E.coli and one strain of Salmonella typhimurium were highly susceptible to both the bactericidal and the permeability enhancing effects of granulocyte fractions, whereas two strains of Serratia marcescens and one strain of Pseudomonas aeruginosa were resistant to both effects. Another strain of P. aeruginosa was rendered susceptible to actinomycin D without being killed and two strains of S. typhimurium remained insensitive to actinomycin D while being killed by granulocytes.
PROPERDIN FACTOR D
Authors: Fearon Douglas T. , Austen K. Frank , Ruddy Shaun
Published: June 2004

The protein in the properdin pathway responsible for conversion of precursor factor D to D has been isolated and found to be identical with properdin. Sequential ion exchange and gel filtration chromatography demonstrated identity between properdin protein, measured by radial immunodiffusion, and the capacity to activate D to D, assessed by formation of the intermediate, EAC43B(D). Properdin, purified in this manner, was homogeneous on acid polyacrylamide disc gel electrophoretic analysis, with the band of protein corresponding to the position of eluates in the replicate gel capable of activating highly purified D. Demonstration of the homogeneity of purified D by alkaline disc gel electrophoresis, coupled with the linear stoichiometric hemolytic titrations of each factor, indicates that direct interaction between properdin and D generates D. Thus, activation of D by properdin represents a mechanism in the properdin pathway by which D becomes available for formation of the C3b-dependent C3 convertase.
SPECIFIC BINDING OF NERVE GROWTH FACTOR (NGF) BY MURINE C 1300 NEUROBLASTOMA CELLS
Authors: Revoltella R. , Bertouni L. , Pediconi M. , Vigneti E.
Published: June 2004

Murine C 1300 neuroblastoma cells bind with high avidity on their membrane surface the nerve growth factor (NGF), a protein capable of inducing differentiation of sympathetic nerve cells. The total binding capacity of NGF by the cells was quantitatively measured by a radioimmunoassay technique, using 125I-labeled NGF. An average number of about 106 molecules of NGF could be bound, at saturation, by each cell with an average relative association constant of about 107 liters/mol. Using synchronized cells, it was found, however, that either the number of molecules of ligand bound or the avidity of the binding interaction between NGF and cells varied depending upon their growth cycle, the maximal-binding occurring during the G1 and early S phase. Binding of [125I]NGF was suppressed by trypsin treatment of the cells, however new receptor sites were rapidly replaced onto the membrane surface within 1–2 h. Cells exposed to 3 M KCl released into the supernate a protein product exhibiting similar high avidity for NGF. Acrylamide gel electrophoresis suggested a restricted molecular heterogeneity of this product, with a major component in the 52,000 mol wt region. Antibodies made specific to this protein were capable, in the absence of the complement, of inhibiting the binding of [125I]NGF by the cells and in the presence of the complement they killed them.
IMMUNOLOGICAL FUNCTIONS OF HUMAN T-LYMPHOID CELL LINE (MOLT)
Authors: Takada Akikazu , Takada Yumiko , Minowada Jun
Published: June 2004

A short term incubation of the mixture of established human T-lymphoid cells (MOLT) and sheep red blood cells (SRBC) resulted in the release of factors which nonspecifically suppressed the response of mouse spleen cells against heterologous erythrocytes in vitro. Neither human B-cell line (RPMI 1788), nor the supernate of MOLT cell suspension in the absence of SRBC had such suppressive effects.

The supernate of the mixture of MOLT cells with chicken red blood cells (CRBC) did not suppress either anti-CRBC or anti-SRBC responses of mouse spleen cells. Since CRBC did not form rosettes with MOLT cells, it is suspected that the origin of the production of these factors might be MOLT cells forming SRBC rosettes. Some of these factors are dialysable.
FORMATION AND BIOLOGIC ROLE OF POLYOMA VIRUS-ANTIBODY COMPLEXES
Authors: Oldstone Michael B. A. , Cooper Neil R. , Larson David L.
Published: June 2004

Interaction of polyoma virus, specific antibody, and complement has been studied. Firm evidence has been gathered that C1 through C3 and not C5 through C9 enhance neutralization of virus-antiviral antibody (V-Ab) complexes. C enhancement of neutralization occurs primarily by agglutination of V-Ab complexes and not by virion lysis or attachment of large protein molecules to the V-Ab complex. In this model, binding of C1, 4, 2, 3 to the V-Ab complex may explain why some viruses concentrate in or infect certain cells bearing C3 receptors such as B lymphocytes, macrophages, and monocytes.
THE ROLE OF HUMORAL ANTIBODY IN THE REJECTION OF PRIMARY RENAL ALLOGRAFTS IN SHEEP
Authors: Pedersen Niels C. , Morris Bede
Published: June 2004

Antibody which had cytotoxic and agglutinating activity against donor lymphocytes appeared in the blood stream of primary renal allograft recipients usually within 48 h of the graft being finally rejected. Appearance of the antibody

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in the blood was associated with severe alterations in vascular permeability and this led to increases in the numbers of red cells and in the protein content of the lymph coming from the allograft. It was possible to elute cytotoxic and agglutinating antibody from renal allograft tissue, showing that this type of antibody was bound to graft antigens during the rejection process. The transfusion of whole serum or serum globulins obtained from sheep that had previously rejected allografts led to the destruction of recently installed renal grafts and the histological changes produced in these grafts and the alterations in the composition of the lymph coming from them were similar to those seen in the terminal stages of primary rejection. These findings have led us to the conclusion that in the sheep, at least the terminal stage of primary renal allograft rejection is mediated by humoral antibody.
INTERACTIONS OF C-REACTIVE PROTEIN WITH THE COMPLEMENT SYSTEM
Authors: Siegel Joan , Rent Rosemarie , Gewurz Henry
Published: June 2004

Protamine sulfate was found to consume large amounts of C selectively during preincubation with sera of individuals in the "acute phase". Marked depletion of C1, C4, and C2 with minimal, if any, depletion of C3-9, was observed. The consumption was time and temperature dependent, occurring most rapidly and extensively at 37°C, 0.10 M relative salt concentration and pH 7.5–8.0; it required calcium ions. It was mediated by a heat-stable nondialyzable factor which separated with C-reactive protein (CRP) during fractionation and purification, correlated with serum CRP levels, and, like other known reactivities of CRP, was inhibited by phosphoryl choline. Preparations of CRP purified either from serum or ascites resulted in consumption of large amounts of C1, C4, and C2 when preincubated with normal serum and protamine. We conclude that CRP is a potent activator of the C system at the level of C1, and that polycations such as protamine sulfate are substrates of CRP which can bring about this activation. It seems not unlikely that one role of CRP in health and disease involves its ability to interact with the C system.
GENETIC CONTROL OF IMMUNE RESPONSES IN VITRO
Authors: Kapp Judith A. , Pierce Carl W. , Schlossman Stuart , Benacerraf Baruj
Published: June 2004

In recent studies we have found that GAT not only fails to elicit a GAT-specific response in nonresponder mice but also specifically decreases the ability of nonresponder mice to develop a GAT-specific PFC response to a subsequent challenge with GAT bound to the immunogenic carrier, MBSA. Studies presented in this paper demonstrate that B cells from nonresponder, DBA/1 mice rendered unresponsive by GAT in vivo can respond in vitro to GAT-MBSA if exogenous, carrier-primed T cells are added to the cultures. The unresponsiveness was shown to be the result of impaired carrier-specific helper T-cell function in the spleen cells of GAT-primed mice.

Spleen cells from GAT-primed mice specifically suppressed the GAT-specific PFC response of spleen cells from normal DBA/1 mice incubated with GAT-MBSA. This suppression was prevented by pretreatment of GAT-primed spleen cells with anti-θ serum plus C or X irradiation. Identification of the suppressor cells as T cells was confirmed by the demonstration that suppressor cells were confined to the fraction of the column-purified lymphocytes which contained θ-positive cells and a few non-Ig-bearing cells. The significance of these data to our understanding of Ir-gene regulation of the immune response is discussed.
SPECIFIC POSITIVE SELECTION OF LYMPHOCYTES REACTIVE TO STRONG HISTOCOMPATIBILITY ANTIGENS
Authors: Howard Jonathan C. , Wilson Darcy B.
Published: June 2004

Selected populations of thymus-derived (T) rat lymphocytes having specific immunological reactivity to chosen histocompatibility (H) alloantigens are found among the cellular products of the mixed lymphocyte interaction (MLI). Such specific selection seems to depend on (a) the antigen-induced proliferation of specific H antigen reactive cells (HARC), and (b) the disappearance of nonreactive cells from the cultures. When the surviving cells from this lymphocyte-antigen interaction are transferred into thymectomized, X-irradiated, marrow-reconstituted syngeneic recipients (B rats) which lack detectable T-lymphocyte functions, the lymphocyte populations subsequently recovered from the hosts possess the capacity to react in the MLI and in the graft-vs.-host (GVH) reaction, and the reactions have specificity for the original priming alloantigens. In addition, these findings identify the cell that reacts in the MLI with the GVH reactive cell.
CLONAL NATURE OF THE IMMUNE RESPONSE TO PHOSPHORYLCHOLINE
Authors: Claflin J. Latham , Davie Joseph M.
Published: June 2004

A new idiotypic determinant(s) on mouse anti-PC antibodies is described. Antibodies to the determinant(s) were raised in rabbits by immunization with HOPC 8, a PC-binding myeloma protein, and were isolated from HOPC 8 immunoadsorbent by elution with PC. These antibodies react with binding site determinants on anti-PC antibodies raised in all 15 inbred mouse strains tested regardless of histocompatibility or allotype, but fail to react with antibodies of other specificities or with anti-PC antibodies raised in other rodent species. These results correlate closely with other studies which show similar binding specificity of anti-PC antibodies raised in 17 different strains of mice. The site-associated idiotypic determinant(s) is clearly distinct from that detected by mouse anti-HOPC 8 antisera. This latter determinant(s) is present on anti-PC antibodies of only a few strains of mice and may not be in the binding site.
IN VITRO GENERATION OF MEMORY LYMPHOCYTES REACTIVE TO TRANSPLANTATION ANTIGENS
Authors: Hollander Nurit , Ginsburg Haim , Feldman Michael
Published: June 2004

The in vitro generation of memory cells reactive to transplantation antigens is described. Blast cells, obtained from rat lymphocytes sensitized on xenogeneic or allogeneic fibroblast monolayers, reverted to secondary small lymphocytes after transfer from the foreign sensitizing to syngeneic monolayers. These secondary small lymphocytes had a limited in vitro life span of 4–6 wk. They manifested properties of memory cells: upon re-exposure to fibroblasts of the sensitizing phenotype, the secondary lymphocytes adhered to the fibroblast monolayer and transformed into blast cells with cytotoxic activity. The response of secondary lymphocytes was rapid, compared to that of normal lymphocytes, and directed specifically against the primary sensitizing antigens.
INDEPENDENT SYNTHESIS OF LIGHT AND HEAVY CHAINS
Authors: Laskov Reuven , Scharff Matthew D.
Published: June 2004

The rates of immunoglobulin synthesis have been examined in two MFC-11 cell lines which were independently adapted to tissue culture and in light-chain-producing variants derived from each of them. One cell line synthesized 2.5 pg immunoglobulin/cell/h, while the other synthesized 3.6 pg immunoglobulin/cell/h. The ratio of heavy and light chains in the two cell lines was approximately the same, and the size of the intracellular pool of immunoglobulin was proportioned to the rate of synthesis. Variants which had spontaneously lost the ability to produce heavy chains continued to synthesize light chains at approximately the same rate as their parent cell line.
SEROLOGICAL DISTINCTION OF MUTANTS B6.C-H(z1) AND B6.M505 FROM STRAIN C57BL/6
Authors: Klein Jan , Hauptfeld Miroslav , Hauptfeld Věra
Published: June 2004

A quantitative serological difference was found between strains Hz1 and M505 carrying mutant H-2 haplotypes ba and bd, respectively, and the original strain B6(H-2b). The finding suggests that the mutations occurred in the H-2Kb gene, and together with data on MLR and CML challenges the current concept of H-2 regions' involvement in immune reactions.
LIGAND-INDUCED MOVEMENT OF LYMPHOCYTE MEMBRANE MACROMOLECULES
Authors: Unanue Emil R. , Karnovsky Morris J.
Published: June 2004

Capping of surface Ig by anti-Ig antibodies involves a membrane perturbation requiring an energy-dependent step. Lymphocytes treated with anti-Ig are stimulated to move. Previously, we had shown that movement was not essential for capping, although it influenced the localization of the cap. We have investigated the role of cell movement and of microtubular proteins in this phenomenon. Treatment of B lymphocytes with colchicine does not affect capping of Ig nor does it affect the increase in translational movement produced by anti-Ig antibodies. Treatment of lymphocytes with cytochalasin B stops translational movement and may affect capping to some degree under appropriate circumstances. Lymphocytes treated with both drugs are impaired in capping. We surmise that there may be two cytoplasmic events regulating directly or indirectly capping: one associated with the process of translational movement, the other associated with the activity of microtubules. Lymphocytes treated with concanavalin A do not cap Ig. Colchicine reverses this inhibition. Certain experimental procedures antagonize the colchicine effect, the most striking of which is the use of cytochalasin B. Colchicine appears to increase movement of the Con A-treated lymphocyte, and this increased movement appears responsible for the accumulation of complexes to the posterior part of the cell. Con A inhibits patching of Ig by anti-Ig, and this is not reversed by colchicine.
BINDING OF SOLUBLE IMMUNE COMPLEXES TO HUMAN LYMPHOBLASTOID CELLS
Authors: Theofilopoulos Argyrios N. , Wilson Curtis B. , Bokisch Viktor A. , Dixon Frank J.
Published: June 2004

Cells from a human lymphoblastoid cell line (Raji), with B-cell characteristics, and having receptors for human IgG Fc, C3b, and C3d, were used in an immunofluorescence test as in vitro detectors of immune complexes in animal and human sera. By this test, as little as 200–300 ng aggregated human gamma globulin or immune complexes per ml serum could be detected. The receptors for IgG Fc on the Raji cells were shown to be inefficient in detecting aggregated human gamma globulin and binding of aggregates to these receptors was inhibited by physiologic concentrations of 7S human IgG. Enhancement of aggregated human gamma globulin binding and binding of immune complexes formed in vitro to Raji cells was observed when the receptors for complement on these cells were used. By using the receptors for complement on Raji cells, circulating immune complexes were detected in rabbits with acute serum sickness, in mice with acute lymphocytic choriomeningitis virus infection, and in humans with immune complex type glomerulonephritis. The Raji cell test may be useful in detecting complement fixing immune complexes in different disease states, in monitoring circulating complexes in patients with immune complex diseases and in identifying the antigen(s) responsible for the induction of pathogenic immune complexes in humans and animals.
A NEW SENSITIVE ASSAY FOR ANTIBODY AGAINST CELL SURFACE ANTIGENS BASED ON INHIBITION OF CELL-DEPENDENT ANTIBODY-MEDIATED CYTOTOXICITY
Authors: Halloran Phil , Schirrmacher Volker , Festenstein Hilliard
Published: June 2004

Inhibition of cell-dependent antibody-mediated cytotoxicity has been investigated as a new assay for antibody against cell surface antigens. The cytotoxicity system consisted of effector cells (normal mouse spleen cells), target cells (61Cr-labeled chicken erythrocytes), and antitarget cell antibody. Addition of antibody against cell surface antigens in the effector cell population regularly inhibited the cytotoxicity measured in this system. This cytotoxicity inhibition assay (CIA) detected antibody with a variety of specificities: anti-H-2, anti-Thy 1.2, anti-immunoglobulin, and antimouse bone marrow-derived lymphocyte antigen. When the inhibition by anti-H-2 sera was analyzed using effector cells from congenic mice, the activity was found to be directed against specificities mapping in the H-2K, H-2D, and I regions of the H-2 complex, correlating well with the specificities characterized by complement-dependent assays.

A comparison between the sensitivity of the CIA and complement-dependent lysis revealed that the CIA was 2–11 times more sensitive for anti-H-2 antisera and 20–780 times more sensitive for certain antisera against subpopulations of the spleen cells (i.e., T cells or B cells). The CIA proved to be precise, sensitive, and reliable. It may become a very useful antibody assay in various species including man.
EFFECTS OF CONCANAVALIN A ON MOUSE PERITONEAL MACROPHAGES
Authors: Edelson Paul J. , Cohn Zanvil A.
Published: June 2004

The half-time for the degradation of horseradish peroxidase (HRP) is increased from 14 h to 37 h in Con A-treated cells, while the half-time for the degradation of [125I]BSA is increased from 5.4 h to 14.8 h. This supports prior microscopic observations which suggested that Con A pinosomes showed a marked impairment in their ability to form phagolysosomes. Artifacts due to anomalous behavior of HRP-Con A complexes, or to inhibition of lysosomal hydrolases by Con A, could be excluded.

These indications of impaired phagolysosome formation, as well as those described in the preceding paper, could be reversed by postincubation of the cells in mannose, but not in galactose. This reversal is accompanied by a dissociation of Con A-FITC from the inner surface of the pinosome membrane, into the vesicle contents. These observations may be relevant to the ability of Con A to affect several membrane characteristics, and are also of interest in relation to the impaired formation of phagolysosomes which has been described in certain in vitro parasitic infections of macrophages or other cells.
HOST GENETIC CONTROL OF RECOVERY FROM FRIEND LEUKEMIA VIRUS-INDUCED SPLENOMEGALY
Authors: Chesebro Bruce , Wehrly Kathy , Stimpfling Jack
Published: June 2004

The influence of the major mouse histocompatibility gene complex (H-2) on the response of mice to Friend leukemia virus was studied in F1 congenic mice differing only at genes within the H-2 complex. F1 mice which were H-2b/b had a high incidence of recovery from splenomegaly compared to H-2b/d or H-2b/a mice. In mice with recombinations within the H-2 complex a gene (designated RFV-1), responsible for the Friend virus recovery effect, was found to map near or within the D region of serologically detectable transplantation antigens. Because the incidence of recovery was much higher in F1 H-2b/b mice than in parental H-2b/b mice, other non-H-2 host genetic factors also appear to be important to expression of recovery in H-2b/b F1 mice. The mechanisms of action of these genes remain unknown.
EXPERIMENTAL STUDIES ON THE BRIDGING HYPOTHESIS OF ANAPHYLAXIS
Authors: Mossmann Horst , Meyer-Delius Margot , Vortisch Uta , Kickhöfen Botho , Hammer Dietrich K.
Published: June 2004

The present study has established, that cows suitably immunized with either DNP-edestin (DNP-Ed), di-DNP-gramicidin-J [(DNP)2-Gram], respectively, or p-azobenzenearsonate-Ed (ABA-Ed) synthesized and secreted reaginic antibodies (IgE) into colostrum. Whereas ABA-Ed failed to elicit more than a low response, there was however a persistent and increased antibody synthesis between 10 and 56 days after priming with DNP-Ed.

Bivalent and multivalent DNP haptens differing in molecular size, degree of substitution, and rigidity were compared for their effectiveness in eliciting Prausnitz-Küstner (P-K) reactions in either newborn colostrum-deprived calves or in those 4 wk of age. The sensitization with reaginic anti-DNP antibody has been accomplished either by feeding colostrum of the immunized dam or by intradermal injection of reaginic serum or colostral whey. It could be demonstrated that equimolar doses of the bivalent α,N-(ϵ,N-DNP-aminocaproyl-)-ϵ,N-DNP-L-lysine and the multivalent dinitrophenylated bovine serum albumin were equally effective in eliciting reactions in skin sites provided that a high affinity antibody was used for sensitization. By contrast, the comparatively rigid, bivalent hapten, (DNP)2-Gram consistently failed to induce comparable reactions. Furthermore, it was clearly shown that optimal distances of determinant groups on the haptenic molecule are a prerequisite for positive P-K reactions, since α,ϵ,N-bis-DNP-lysine failed to induce comparable reactions.

Concurrent sensitization of skin sites with reaginic anti-DNP and anti-ABA antibodies provides the final proof that cross-linking of two adjacent reaginic molecules on the mast cell surface by a bivalent hapten is required for effective elicitation of immediate-type reactions. This has been accomplished by utilizing the bivalent ϵ,N-DNP-α,N-[(4-hydroxy-3-azobenzenearsonic acid)-phenacetyl]-L-lysine (DNP-ABA) carrying noncross-reactive haptenic groups, which was consistently effective in eliciting P-K reactions in doubly but never in singly sensitized skin sites. It is apparent from the results that equimolar doses of monovalent haptens could completely inhibit the response to DNP-ABA. The present studies finally establish that mast cells of newborn colostrum-deprived calves lack IgE molecules on their surface. Thus, mast cells of newborn calves may be unique, to investigate the molecular mechanisms involved in immediate-type reactions more precisely.
PROTECTIVE AND CELLULAR IMMUNE RESPONSES TO IDIOTYPIC DETERMINANTS ON CELLS FROM A SPONTANEOUS LYMPHOMA OF NZB/NZW F1 MICE
Authors: Sugai Susumu , Palmer Donald W. , Talal Norman , Witz Isaac P.
Published: June 2004

A spontaneous lymphoma (141) producing monoclonal IgM is established in NZB/NZW F1 (B/W) mice who spontaneously develop an autoimmune disease. Idiotypic determinants of 141 IgM are present on the lymphoma cell surface as shown by indirect immunofluorescence and specific cytotoxicity with rabbit anti-idiotypic antiserum. Fluorescence and cytotoxicity are inhibited by 141 IgM but not by 104E IgM, a monoclonal IgM produced by a BALB/c plasmacytoma.

Immunization of B/W mice with 141 IgM before transplantation of lymphoma 141 confers protective immunity. No such protection occurs after immunization with 104E IgM or other unrelated proteins. Protected mice contain spleen cells cytotoxic for 141 lymphoma cells. This cytotoxicity is blocked by incubation of spleen cells with 141 IgM but not with 104E IgM. Moreover, splenic lymphocytes from protected mice are stimulated to synthesize DNA by 141 IgM but not by 104E IgM. These results suggest that specific cellular immune responses to idiotypic determinants may participate in the observed protection against challenge with the corresponding B-cell tumor.
ANTIGEN-SPECIFIC T-CELL FACTOR IN CELL COOPERATION: PHYSICAL PROPERTIES AND MAPPING IN THE LEFT-HAND (K) HALF OF H-2
Authors: Munro A. J. , Taussig M. J. , Campbell Rosalie , Williams Heather , Lawson Yvonne
Published: June 2004

Mouse thymus cells, educated to poly(tyrosyl,glutamyl)-polyDLalanyl--polylysyl [(T,G)-A--L], release an antigen-specific factor on brief culture in vitro. The factor cooperates with bone marrow cells in the antibody response to (T,G)-A--L in irradiated recipients. Its mol wt determined from Sephadex G100 chromatography is in the region of 50,000. The factor is removed by specific antigen-coated columns, but not by anti-immunoglobulin (anti-Fab, anti-µ, anti-Fv) adsorbents. The factor is removed by alloantisera directed against the H-2 haplotype of the strain in which it is produced. Moreover, only antisera with specificity for the K side of H-2 were successful in removing the factor activity.
IMMUNOLOGICAL RESPONSES OF MICE TO NATIVE PROTOPLASMIC POLYSACCHARIDE AND LIPOPOLYSACCHARIDE
Authors: von Eschen Kenneth B. , Rudbach Jon A.
Published: June 2004

Functional separation of the two signals involved in stimulating immunological responses was achieved through the judicious use of two natural bacterial antigens. Native protoplasmic polysaccharide (NPP) extracted from Escherichia coli was immunochemically identical to the lipopolysaccharide (LPS) extracted from the same organism. However, NPP was not endotoxic, not mitogenic, did not fix complement, and was immunologically independent of T cells. The NPP, which appeared to contain only the antigenic signal, could induce a primary antibody response in mice and could sensitize mice for a secondary response. However, the antigenic signal contained in NPP was insufficient to trigger a secondary response in mice primed with either NPP or LPS. LPS, containing both the antigenic and second signals, was required to trigger a secondary response in primed mice.
SYNERGY BETWEEN SUBPOPULATIONS OF MOUSE SPLEEN CELLS IN THE IN VITRO GENERATION OF CELL-MEDIATED CYTOTOXICITY
Authors: Hodes Richard J. , Handwerger Barry S. , Terry William D.
Published: June 2004

Two subpopulations separated from normal spleen have been shown to synergize as responding cells in the in vitro induction of specific cell-mediated cytotoxicity during the mixed lymphocyte culture (MLC). The synergizing populations are a nylon wool column-adherent and a nylon wool column-nonadherent fraction, enriched for B lymphocytes and T lymphocytes, respectively. When a mixture of these fractions is used as the responding cell population in MLC, greater cytotoxicity is generated than would be expected from the sum of activities generated in the two subpopulations sensitized separately. The synergy appears to occur at the sensitization rather than the effector phase. The synergizing cell which is contained in the nylon-adherent subpopulation is distinct from the cytotoxic effector T lymphocyte, is resistant to lysis by rabbit antimouse brain serum, and is unresponsive to phytohemagglutinin; its synergizing function could not be replaced by either plastic-adherent spleen cells or peritoneal exudate cells. These results suggest a role of a non-T-cell nonmacrophage population in the generation of cytotoxic activity.
The oncornavirus glycoprotein gp69/71: a constituent of the surface of normal and malignant thymocytes.
Authors: Del Vellano B C , Nave B , Croker B P , Lerner R A , Dixon F J
Published: June 2004

The oncornavirus related proteins associated with the surface of normal and malignant thymocytes were studied. Three virion-associated proteins (gp69/71, p45, p30) were associated with lymphoma cells from about 70% of the tumors studied. Two virion-associated proteins (gp69/71 and p45 were associated with normal thymocytes form some but not all strains of mice. In gp69/71- mice, conversion to the gp69/71+ phenotype accompanied leukemogenesis. An interesting difference in the apparent molecular size of virus related antigens of the 70,000 dalton size class was detected in lymphoma cells present in involved spleens as compared to involved thymuses. Mice infected as neonates with Scripps leukemia virus make antibody to gp69/71 and some make antibodies to molecules associated with the surface of their own tumors. The significance of the restricted presence of antigens coded for by the viral genome to the surface of some differentiated cells is discussed in reference to (a) the relationship between virion, leukemia associated, and differentiation dependent markers, and (b) the possible consequence to the host of having similar antigenic determinants on three independent structures with replicative potential (virus, normal thymocytes, and tumor cells).
Relation of GIX antigen of thymocytes to envelope glycoprotein of murine leukemia virus.
Authors: Obata Y , Ikeda H , Stockert E , Boyse E A
Published: June 2004

Expression of Gix surface antigen on thymocytes is an inherited mendelian train of certain strains of mice. We report here the following new findings: (a) Gix antigen was found free in the serum of Gix+ mouse strains. (b) Expression vs. nonexpression of Gix antigen was invariably correlated with presence or absence of the group-specific antigen of Murine leukemia virus (MuLV) gp69/71 in the serum of mice of inbred and segregating populations. (c) Gix antigen could be removed from normal Gix+ mouse serum by precipitation with antiserum to MuLV gp 69/71. (d) Anti-gp69/71 serum was weakly cytotoxic for Gix+ thymocytes, and partially blocked the cytotoxic activity of Gix antibody for Gix+ thymocytes. (e) Purified AKR virus absorbed Gix activity, and disruption of the virions did not increase their absorbing capacity. These serological data indicate that Gix antigen is a constituent of gp69/71, the glycoprotein which is the major component of the MuLV envelope. On present evidence, Gix antigen is represented in intact virions and is probably accessible to Gix antibody.
Biochemical evidence linking the GIX thymocyte surface antigen to the gp69/71 envelope glycoprotein of murine leukemia virus.
Authors: Tung J S , Vitetta E S , Fleissner E , Boyse E A
Published: June 2004

It is known that the thymocyte surface antigen GIX is found in some strains of mice and not others, and that its expression in mice of strain 129, in which most extensive genetic studies have been made, is controlled by two unlinked cellular chromosomal loci. We have now isolated a protein with a mol wt of approximately 70,000 daltons from the surface of thymocytes from 129 mice, which have antigenic and biochemical properties characteristic of the gp69/71 envelope component of murine leukemia virus. Our evidence is compatible with the conclusion that it carries the GIX antigen.
The specificity of cellular immune responses in guinea pigs. I. T cells specific for 2,4-dinitrophenyl-o-tyrosyl residues.
Authors: Janeway C A , Cohen B E , Ben-Sasson S Z , Paul W E
Published: June 2004

Guinea pigs immunized with the hapten 2,4-dinitrophenyl (DNP) coupled directly to Mycobacterium tuberculosis of strain H37Ra (DNP-H37) show a variety of cell-mediated immune responses to DNP coupled to protein carriers. The cells responsible for this specific response are thought to be T lymphocytes for the following reasons: Guinea pigs immunized with DNP-H37 displayed delayed hypersensitivity reactions to several DNP-proteins and contact sensitivity to dinitrofluorobenzene. Peritoneal exudate lymphocytes (PELs) obtained from DNP-H37 immune animals respond to DNP-proteins with DNA systhesis and cause inhibition of macrophage migration. PELs are highly enriched in T lymphocytes and contain few immunoglobulin-bearing cells. Further depletion of immunoglobulin-bearing cells from this population does not diminish the in vitro proliferative response to antigen. Nitrophenyl conjugates of proteins lacking a paranitro group stimulated DNA synthesis poorly or not at all, indicating the importance of the paranitro group of DNP in antigen recognition by T cells in this system. In this respect, the specificity of T cells resembles that of DNP-specific antibody from the same animals. On the other hand, DNP conjugates of copolymers of glutamic acid and lysine and DNP conjugated to proteins via an interposed beta-alanyl-glycyl-glycyl spacer failed to stimulate DNA synthesis, although such compounds bind very efficiently to anti-DNP antibody. By contrast, DNP conjugates of synthetic polypeptide carriers containing as little as 7% tyrosine strongly stimulated DNA synthesis in DNP-H37 immune PELs. That the determinant responsible for this stimulation was DNP coupled to the hydroxyl group of tyrosine was shown by selective removal of DNP from tyrosine by thiolysis with 2-mercaptoethanol, which abolished their ability to stimulate T cells.
The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis.
Authors: Watson J
Published: June 2004

The intracellular ratio of adenosine 3',5'-cyclic monophosphate (cyclic AMP) to guanosine 3',5'-cyclic monophosphate (cyclic GMP) may control the developmental pathway followed by antibody-forming cell (AFC) precursors. The evidence for this is derived from several different types of experiments. First lipopolysaccharide (LPS) which is mitogenic for B lymphocytes, stimulates rapid, transient changes in intracellular levels of cyclic GMP but not cyclic AMP when added to mouse spleen cultures. Cyclic GMP itself stimulates DNA synthesis in these cultures, suggesting that the intracellular changes in cyclic GMP levels are involved in the mitogenic signal delivered by LPS to cells. The absolute amounts of cyclic nucleotides may vary widely in different cells under various conditions, however, the intracellular ratio of cyclic AMP to cyclic GMP is always high in nondividing cells and low in dividing cells. AFC precursors appear to respond to antigen in the absence of T-cell activity by inactivation (1-7). In the response to antigen in the presence of specific T cells, precursor cells proliferate and mature to AFC. Raising intracellular levels of cyclic AMP inhibits cell proliferation and leads to precursor cell inactivation (14, 15). It is suggested that the interaction of antigen with immunoglobulin receptors on the surface of precursors cells leads to the stimulation of adenylate cyclase activity and initiates the inactivation pathway. Since cyclic GMP stimulates immune responses in T-cell-depleted cultures (14, 15) and increasing cyclic GMP levels appear to be involved in the delivery of a mitogenic signal to cells, it is suggested that T-helper cells deliver a signal to precursor cells via the stimulation of guanylate cyclase to initiate the inductive pathway. It is suggested that it is the intracellular ratio of cyclic AMP to cyclic GMP that regulates the fate of precursor cells, not the absolute level of one cyclic nucleotide.
The presence of IgA on the surface of rat thoractic duct lymphocytes which contain internal IgA.
Authors: Williams A F , Gowans J L
Published: June 2004

The presence of lymphocytes with internal IgA among cells from rat thoracic duct lymph wdy. The number of cells detected was greater in animals kept in a convential animal house compared with those maintained under specific pathogen-free conditions. Thoracic duct lymph from B rats and adult thymectomized rats also contained cell with internal IgA. The surface Ig of the IgA-containing cells was studied using a double-labeling technique with (126I) anti-Ig to detect surface Ig, and fluorescein-conjugated anti-IgA in large amounts, but very little IgM and no surface IgG2. The surface IgA was not acquired passively.
Sequential responses of mouse spleen T cells in mixed lymphocyte culture-induced cytolysis.
Authors: Häyry P , Andersson L C
Published: June 2004

T cells triggered to blast transformation and proliferation by histoincompatible cells have the capacity of reverting "back" to lymphocytes. These "secondary" lymphocytes and their progeny cells are able to respond repeatedly to the same allogeneic stimulus in vitro.
Rosette-forming ability of thymus-derived lymphocytes in cell-mediated immunity. I. Delayed hypersensitivity and in vitro cytotoxicity.
Authors: Elliott B E , Haskill J S , Axelrad M A
Published: June 2004

Effector cells in delayed hypersensitivity and in vitro cytotoxicity were studied in lymph node cells from animals immunized with sheep erythrocytes (SRBC) in complete Freund's adjuvant. Delayed hypersensitivity response (DHR) was assayed by the increase in foot pad swelling after the intrafoot pad injection of immune cells plus antigen. Cell-mediated cytotoxicity against SRBC was assayed by a microcytotoxicity test with sheep fibroblasts as target cells. Effector cells were antigen specific, sensitive to anti-theta serum plus complement (C), and insensitive to anti-Ig serum plus C. A nonrosette-forming (non-RFC) small lymphocyte effector T cell and a rosette-forming medium lymphocyte effector T cell were isolated by velocity sedimentation. The small lymphocyte non-RFC required a longer time than the medium lymphocyte RFC effector cell to produce maximum activity. Buoyant density failed to distinguish medium lymphocyte effector cells in DHR and in vitro cytotoxicity.
Rosette-forming ability of thymus-derived lymphocytes in humoral and cell-mediated immunity. II. Helper cell activity.
Authors: Elliott B E , Haskill J S
Published: June 2004

The technique of velocity sedimentation at unit gravity was used to determine the size and rosette-forming ability of helper cells in nonimmune and immune C57BL/6 mice. Helper T cells were assayed by the ability to cooperate with bone barrow (B) cells in the antibody response to sheep erythrocytes (SRBC) in vivo. 19S helper cells in nonimmune animals were nonrosette-forming small lymphocytes; after immunization with SRBC in complete Freund's adjuvant, 19S helper cells were nonrosette-forming medium lymphocytes. 7S helper cells in immune animals were small lymphocytes which did not form rosettes. No SRBC binding by helper cells was observed under the conditions of rosette formation used.
Separation of antigen-specific lymphocytes. II. Enrichment of hapten-specific antibody-forming cell precursors.
Authors: Haas W
Published: June 2004

Normal spleen cells were separated in dishes coated with thin layers of DNP-gelatin or NIP-gelatin into binding and nonbinding cells and stimulated in vitro with DNP- and/or NIP-conjugated polymerized flagellin (POL). Hapten-specific unresponsiveness was induced in the binding cell population by melting the gel at 37 degrees C or in unfractionated cells by pretreatment with soluble hapten-gelatin and could be reversed by treatment with collagenase. A specific enrichment of anti-DNP and anti-NIP antibody-forming cell precursors (AFCP) could be demonstrated in the binding cell populations after treatment with collagenase in cultures with or without "feeder" cells. However, the response of small numbers of unfractionated and purified hapten-specific spleen cells was suboptimal even in the presence of mitomycin-treated or irradiated feeder cells. Optimal numbers of anti-DNP (anti-NIP) antibody-forming cells were generated by small numbers of normal or purified spleen cells in the presence of spleen cells depleted of anti-DNP (anti-NIP) AFCP. In this system the response of only 2 times 10-4 purified hapten-specific cells was higher than the response of 10-6 unfractionated cells. Purified DNP-specific cells responded only to DNP-POL but not to NIP-POL and purified NIP-specific cells responded only to NIP-POL but not to DNP-POL. The degree of enrichment of anti-DNP AFCP decreased with increasing numbers of binding cells. NIP3-gelatin layers bound four to five times less spleen cells than DNP2-gelatin layers and the enrichment of anti-NIP AFCP (about 300-fold) was three times greater than the enrichment of anti-DNP AFCP (about 100-fold). The immunological significance of hapten-gelatin binding cells which apparently failed to respond to antigen is discussed.
Specificity of human lymphocyte complement receptors.
Authors: Ross G D , Polley M J
Published: June 2004

Erythrocytes, bone marrow-derived lymphocytes, monocytes, and granulocytes were shown to have a receptor activity for C4. Theis C4 receptor activity was studied in relation to the previously identified C3b and C3d receptors. By assay for inhibition of rosette formation by fluid-phase complement (C), only two different lymphocyte C receptors were demonstrated. The immune adherence receptor, the only one of the two shared in common with erythrocytes, was specific for C4 or the C3c region of C3b, but was unreactive with C3d. The other lymphocyte receptor, the C3d receptor, was specific for C3d fragments, but would also react to a lesser extent with the C3d region of uncleaved C3b. ThC3d receptor did not react with either C3c or C4. This specificity of the C3d receptor allowed certain cells which contained only C3d receptors to form rosettes with EAC1-3b and EAC1-3d, but not with EAC14. However, because C3d receptors bound EAC1-3d or C3d fragments more firmly than they did EAC1-3b or C3b fragments, many other types of cells containing only C3d receptors, formed rosettes with EAC1-3d but not with EAC1-3b. Erythrocytes and those lymphocytes which contained only immune adherence receptors, formed rosettes with EAC14 and EAC1-3D but not with EAC1-3d. A double-label assay was devised for the simultaneous detection of both types of C receptors on individual lymphocytes. This assay involved fluorescence labeling of one of the two C receptors with soluble C fragments in combination with the usual rosette method for labeling the other type of C receptor. With this double-label assay, it was observed that the two different lymphocyte C receptors capped independently and thus were located on different molecules which could each move through the fluid membrane matrix independently of the other.
Evidence for the involvement of the Ss protein of the mouse in the hemolytic complement system.
Authors: Hansen T H , Shin H S , Shreffler D C
Published: June 2004

A significant within-strain correlation has been demonstrated between the levels of Ss and hemolytic complement (C) activity in two Ss-high strains. Mouse serum specifically depleted of Ss by absorption with F(ab')2 fragments of anti-Ss had negligible C activity. In control experiments, Ss-specific antigen-antibody complexes formed with F(ab')2 fragments did not fix rabbit C, and bovine serum albumin-specific antigen-antibody complexes formed with F(ab')2 fragments did not fix mouse C. Therefore the removal of C activity by anti-Ss [F(ab')2] was apparently not due to C fixation. These results suggest that the Ss protein is a necessary component of the C system.
Tolerance induction in B lymphocytes but thymus-dependent antigens. T cells may abrogate B-cell tolerance induction by prevent an antibody response.
Authors: Schrader J W
Published: June 2004

Thymus-dependent protein antigens such as fowl gamma globulin (FGG) and dinitrophenylated-human gamma globulin (DNP-HGG), readily induced tolerance of the B cell in the absence of T cells even when these antigens were not deaggregated. However, when the same doses of antigen were given in the presence of T cells, the B-cell population was shown to be protected from tolerance induction, especially when the antigen was not in a deaggregated form. In this case, there was in fact evidence of a priming effect, manifest in both the B-cell and T-cell populations. The priming effect on the B-cell population was demonstrated by an increased response of mice pretreated with DNP-HGG, upon challenge with DNP conjugated to a heterologous carrier. The priming effect on the T-cell population was evident in a helper effect demonstrated in vitro. However, when euthymic mice which had been pretreated with large doses of FGG or DNP-HGG were challenged with the homologous carrier, the results were different. In this case, there was a profound suppression of the response against the carrier or the hapten on that carrier. Suppressor activity was also demonstrated in vitro and was shown to be sensitive to treatment with anti-theta-serum plus complement. Additionally it was shown that the effector phase of the suppression had a definite nonantigen-specific component. Thus, in pretreated euthymic mice, provided the homologous carrier was present, the response to a heterologous carrier was also suppressed. To account for the observation that nondeaggregated antigens can induce B-cell tolerance in athymic mice, but B-cell priming and T-cell-mediated suppression in euthymic mice, it is proposed that B-cell tolerance occurs when antigen at some critical dose interacts with the B cell in the absence of some second signal. This second signal is normally provided by the macrophage, probably with the assistance of the T cell, and its effect is to divert the result of the interaction of the B cell with antigen towards immunization and away from tolerance induction. When a large dose of an antigen that tends to form aggregates is given to an animal possessing functional T cells, both T-dependent helper and T-dependent suppressor activities are generated, thus accounting for a situation where the B-cell population is immunized, but B-cell activation is suppressed in the presence of the original carrier.