bluuebunny/crossref_metadata_2025 huggingface dataset:
MITOGENIC EFFECT BY LIPOPOLYSACCHARIDE AND POKEWEED LECTIN ON DENSITY-INHIBITED CHICK EMBRYO FIBROBLASTS
Authors: Vaheri Antti , Ruoslahti Erkki , Sarvas Matti , Nurminen Marjatta
Published: June 2004

The B lymphocyte mitogens, bacterial lipopolysaccharide (LPS), pokeweed lectin, and tuberculin, induced proliferation in density-inhibited monolayer cultures of chick embryo fibroblasts. The stimulation was seen both as an early increase in sugar uptake and cell volume and later as an increase in thymidine incorporation and cell number. The concentration of LPS maximally stimulating fibroblasts was remarkably low, about 0.1–1 ng/ml. LPS preparation with very different sugar chains gave quite similar results indicating that the architecture of the hydrophilic carbohydrate part is not critical for the mitogenic effect.
SURFACE MARKERS ON HUMAN B AND T LYMPHOCYTES
Authors: Jondal Mikael , Klein George
Published: June 2004

Human peripheral lymphocytes were investigated for receptors binding Epstein-Barr virus (EBV) because of the regular association of this virus with infectious mononucleosis and Burkitt's lymphoma.

This was done by a cytoadherence technique where virus-producing cells, displaying fresh viral determinants in their cytoplasmatic membrane, were mixed with lymphocytes. Unfractionated lymphocytes were found to adhere to these cells in contrast to column-purified T lymphocytes. The specificity of the binding was confirmed by blocking experiments that showed that sera containing high titers of antibodies directed against the virus could partially inhibit the adherence in contrast to low-titer sera. It is concluded that B lymphocytes, in contrast to T lymphocytes, have receptors for EBV.

In a second line of experiments it was found that established human lymphoblastoid lines that carry the EBV genome had receptors characteristic for B lymphocytes and did not form T-lymphocyte rosettes. In contrast, a line of known T-lymphocyte origin that did not carry the EBV genome had receptors characteristic for T lymphocytes.

EBV-transformed simian lymphoblastoid lines had surface markers indicating a B-lymphocyte origin in contrast to HVS-transformed simian lines that lacked surface immunoglobulin but carried receptors for sheep red blood cells.
SYNERGY DURING IN VITRO CYTOTOXIC ALLOGRAFT RESPONSES
Authors: Wagner Hermann
Published: June 2004

A mouse in vitro allograft system was used to evaluate the concept of T-T interaction in T cell-mediated cellular immunity. In analyzing the responsiveness of thymus-processed lymphocytes as obtained from different tissues, a heretogeneity within T cells was found in regard to their capacity to be immunized in vitro against transplantation antigens. Recirculating T cells were 10–20-fold superior to thymocytes, splenic T cells being intermediate. When few (1.5 x 106) peripheral T cells, in numbers too small to yield good cytotoxic responses, were mixed with 14 x 106 thymocytes and the cell mixture immunized in vitro against cell-bound alloantigens, cytotoxic activity was generated exceeding about 10–20-fold the values that could be explained by a pure additive effect. Synergy occurred also in a mixture of responder T cells derived from CBA (H-2k) and AKR (H-2k) mice. Thus AKR anti-ϕ C3H serum could be used for discriminating between thymus-derived and peripheral T cell-derived cytotoxic lymphocytes (CL). Cytotoxic activity produced during the synergistic interaction between thymocytes and peripheral T cells was about 70% T cell derived, the remainder being thymus derived. The synoptic interpretation of this finding and "limiting dilution" experiments of the responder cells suggested strongly that peripheral T cells provide the major source for precursor cells of CL, thymocytes acting mainly as helper (amplifier) cells.
A CYCLICAL APPEARANCE OF ANTIBODY-PRODUCING CELLS AFTER A SINGLE INJECTION OF SERUM PROTEIN ANTIGEN
Authors: Romball Carole G. , Weigle William O.
Published: June 2004

After a single intravenous injection of rabbits with aggregated HuIgG, IgM- and IgG-plaque-forming cells (PFC) in both the spleens and peripheral blood of rabbits peaked 5, 13, and 21 days after injection, while almost no PFC could be detected on days 8 and 16. The available data suggest that the secondary peaks of PFC (days 13 and 21) resulted from stimulation of memory cells by persisting antigen that was localized in the germinal centers in the spleen. No such persistence of antigen occurred in the lymph nodes, and these lymphoid tissues did not exhibit secondary peaks of PFC.

The identical kinetic patterns for IgM- and IgG-PFC indicate that the major portion of IgG-PFC did not result from IgM-secreting cells switching to IgG synthesis and secretion.

The present data suggest that the antibody produced and present at the site of interaction between committed cells and antigen is responsible for the regulation of antibody synthesis to persisting antigens. Possible cellular events involved in both the regulation and an apparent synchronous appearance of antibody producing cells in the spleens of rabbits were presented.
THE ABILITY OF BACTERIAL LIPOPOLYSACCHARIDE TO MODULATE THE INDUCTION OF UNRESPONSIVENESS TO A STATE OF IMMUNITY
Authors: Louis J. A. , Chiller J. M. , Weigle W. O.
Published: June 2004

Studies were performed to define the cellular parameters involved in the interference with the induction of immunologic unresponsiveness to human gamma globulin (HGG) by bacterial lipopolysaccharide (LPS). Mice which were injected with deaggregated HGG (tolerogen) and with LPS did not become tolerant to that antigen, but rather became primed to a subsequent challenge with immunogen. The ability to prime with tolerogen and LPS was also demonstrated in an adoptive transfer system. The temporal relationship between the injection of tolerogen and that of LPS was critical for priming to occur. The injection of tolerogen and LPS not only primed mice to HGG, but also resulted in a primary antibody response to HGG. The capacity of LPS to interfere with the induction of tolerance was restricted to B cells and did not affect the ability to induce unresponsiveness in T cells. The secondary response to HGG in mice primed by tolerogen and LPS was found to be T-cell independent. These observations are interpreted and discussed from the standpoint of the ability of LPS to circumvent required T-cell cooperation and to modulate to tolerogenic stimulus into an immunogenic signal.
INHIBITORY AND STIMULATORY EFFECTS OF CONCANAVALIN A ON THE RESPONSE OF MOUSE SPLEEN CELL SUSPENSIONS TO ANTIGEN
Authors: Dutton Richard W.
Published: June 2004

The addition of concanavalin A to mouse spleen cell suspensions can either inhibit or stimulate the immune response to heterologous erythrocytes according to the experimental conditions. Evidence is presented which is incompatible with the hypothesis that these two effects are mediated by a single cell and which favors the hypothesis of separate inhibitor and stimulatory cells.
INCREASED REACTIVITY OF MOUSE SPLEEN CELLS SENSITIZED IN VITRO AGAINST SYNGENEIC TUMOR CELLS IN THE PRESENCE OF A THYMIC HUMORAL FACTOR
Authors: Carnaud Claude , Ilfeld David , Brook Itzhak , Trainin Nathan
Published: June 2004

Unprimed mouse spleen cells cultured in vitro on syngeneic tumor cell monolayers have been previously shown to become specifically sensitized and to mediate cytotoxicity against the same type of tumor cells. This complete in vitro system of cell-mediated response has been presently used to test the effect of a thymic humoral factor (THF) upon the differentiation process leading to the generation of specifically committed lymphocytes. Culture media were supplemented with 2% THF during either the sensitization or effector phase, or both phases of the reaction. Whereas the addition of THF during both phases or during sensitization only resulted in a significant increase in the cytotoxicity index, THF added during the effector phase was ineffective. The behavior of unsensitized spleen cells and of spleen cells sensitized against nonrelated transplantation antigens remained unmodified by THF. After showing that the entire reaction is mediated by lymphocytes of thymic origin, THF was directly tested on T or B spleen cells. It was found that only T cells reacted to THF by an increased cytotoxic capacity, while B cells remained inactive after addition of THF. It was therefore concluded that THF activates a postthymic population of lymphoid cells, transforming them into fully competent lymphocytes.
STIMULUS-RESPONSE IN THE MIXED LYMPHOCYTE REACTION
Authors: Harrison Michael R. , Paul William E.
Published: June 2004

Mixed lymphocyte reactions occur when mouse spleen cell populations depleted of thymus-derived (T) lymphocytes are cultured with allogeneic target cells inactivated by mitomycin C or X irradiation, and when F1 hybrid responder cells are cultured with inactivated parental target cells. These responses might be interpreted as indicating that T lymphocytes are not required for responsiveness and that F1 lymphocytes recognize parental alloantigens. Data reported here indicate that the more likely explanation for these surprising results is that inactivated target cells recognize the "responding" cells and this recognition leads to the response observed.
THYMUS INDEPENDENCE OF A COLLAGEN-LIKE SYNTHETIC POLYPEPTIDE AND OF COLLAGEN, AND THE NEED FOR THYMUS AND BONE MARROW-CELL COOPERATION IN THE IMMUNE RESPONSE TO GELATIN
Authors: Fuchs Sara , Mozes Edna , Maoz Arieh , Sela Michael
Published: June 2004

Several inbred mouse strains were screened for their ability to respond to the ordered periodic collagen-like polymer (Pro-Gly-Pro)n, to the random copolymer (Pro66, Gly34)n, to the protein conjugate Pro-Gly-Pro-ovalbumin, to rat tail tendon collagen, rat tail tendon gelatin, and to Ascaris cuticle collagen. Differences were obtained in the magnitude of the antibody titers towards the above immunogens among the strains tested. The level of the response to the ordered polymer (Pro-Gly-Pro)n was not similar to that towards the random (Pro66, Gly34)n, confirming differences in the antigenic determinants of the two immunogens.

The role of the thymus in the immune response to (Pro-Gly-Pro)n and (Pro66, Gly34)n as well as to two collagens and gelatin, was studied in order to find out a possible correlation with the structural features of the immunogens. Heavily irradiated recipients were injected with syngeneic thymocytes, marrow cells, or a mixture of both cell populations and were immunized with the above-mentioned antigens. An efficient immune response to the ordered collagen-like (Pro-Gly-Pro)n was obtained in the absence of transferred thymocytes. The thymus independence of (Pro-Gly-Pro)n was confirmed when thymectomized irradiated mice were used as recipients. In contrast with these results, cooperation between thymus and marrow cells was necessary in order to elicit an immune response to (Pro56, Gly34)n. Similarly, the immune response to the triple helical collagen was found to be independent of the thymus, whereas for an effective response to its denatured product, gelatin, thymus cells were required. These findings indicate that a unique three-dimensional structure of immunogens possessing repeating antigenic determinants plays an important role in determining the need for cell to cell interaction in order to elicit an antibody response.
IMMUNOCHEMICAL STUDIES ON MOUSE MYELOMA PROTEINS REACTIVE WITH DEXTRANS OR WITH FRUCTOSANS AND ON HUMAN ANTILEVANS
Authors: Cisar John , Kabat Elvin A. , Liao Jerry , Potter Michael
Published: June 2004

Four BALB/c IgA mouse myeloma proteins (W3129, W3434, QUPC 52, and UPC 102) reactive with dextran, four myeloma proteins reactive with fructosans, three IgA (W3082, UPC 61, and Y5476), and one IgG2a (UPC 10), and two human antilevans were studied immunochemically. Quantitative precipitin and inhibition assays showed that W3129, W3434, and QUPC 52 had specificities for isomaltose oligosaccharides similar to those previously found with α(1 → 6)-specific human antidextrans. W3129 and W3434 were most complementary to IM5 but W3129 reacted equally with IM4 and IM3 while W3434 had a greater affinity for IM4 than IM3. QUPC 52 had a larger combining region and was most complementary to IM6. Protein UPC 102 (IgA), like MOPC 104E (IgM) (27), was most complementary to the α(1 → 3)-linked trisaccharide, nigerotriose, and thus differed from J558 (29), which was inhibited best by nigeropentaose. UPC 102 was similar to J558 but they differed from MOPC 104E in their reactions with non-α(1 → 3)-linked disaccharides.

The fructosan-specific myeloma proteins fell into two groups with different specificities. The first group, W3082 (IgA), UPC 61 (IgA), and the previously studied J606 (IgG3) (28, 29), reacted with inulin and W3082 and UPC 61 appeared to have identical specificities for ß(2 → 1)-linked fructofuranosyl residues with maximum complementarity for the tetrasaccharide ßDfructofuranosyl (2 → 1)ßDfructofuranosyl(2 → 1)ßDfructofuranosyl(2 → 6)Dglucose while protein J606 was inhibited best by the trisaccharide ßDfructofuranosyl(2 → 1)ßDfructofuranosyl(2 → 6)Dglucose. W3082 and UPC 61 also differed from J606 in their behavior toward sucrose and ßDfructofuranosyl(2 → 6)Dglucose as compared with αDglucosyl(1 → 3)Dfructose (turanose). The second group containing myeloma proteins UPC 10 (IgG2a) and Y5476 (IgA) behaved similarly to human antilevans in that neither reacted with inulin nor were they inhibited by the ß(2 → 1)-linked fructose oligosaccharides. Unlike the ß(2 → 1)-specific proteins, they reacted with perennial rye grass levan that contained over 90% ß(2 → 6)links. The differences in specificity and site size among homogeneous mouse myeloma proteins reactive with the same antigenic determinant are completely consistent with the concept that they represent products of homogeneous clones selected from the known heterogeneous population of antibody-forming cells.
HUMORAL IMMUNOSTIMULATION
Authors: Shearer William T. , Philpott Gordon W. , Parker Charles W.
Published: June 2004

Interaction of microgram quantities of highly purified rabbit anti-TNP antibodies with TNP-substituted HeLa, HEp-2, and L cells caused an intense stimulation of radioactive nucleoside ([125I]UdR and [3H]TdR) uptake which was maximal 24–72 h after exposure of cells to antibody. The stimulation of nucleoside uptake and presumaly DNA synthesis was shown to be immuno logically mediated because unsubstituted cells were not stimulated by anti-TNP antibody, normal rabbit gamma globulin did not stimulate TNP-cells, and a hapten inhibitor, ϵ-DNP-lysine, prevented the stimulation of TNP-cells by anti-TNP antibody. These findings demonstrate that interaction of antibody with cell surface antigen can alter cell membrane transport, and possibly can enhance cell growth.
OCCURRENCE OF SURFACE IgM, IgD, AND FREE LIGHT CHAINS ON HUMAN LYMPHOCYTES
Authors: Fu Shu Man , Winchester Robert J. , Kunkel Henry G.
Published: June 2004

An analysis was made of the immunoglobulin surface markers of the cells of patients with chronic lymphatic leukemia (CLL) in view of previous evidence of their monoclonal B-cell character. The simultaneous presence of IgM and IgD on the surface of the majority of lymphocytes was demonstrated by both immunofluorescence and hemagglutination inhibition in most cases. However, cases were observed with surface IgM without IgD as well as cases with IgD without IgM. IgG and IgA were absent. Studies of the light chains indicated only a single class in a given case. In addition to bound light chains, free light chains were readily demonstrated in most cases through the use of antisera specific for "free chain" determinants. It thus appeared that there are three major types of surface Ig on CLL lymphocytes, IgM, IgD, and free light chains.
LYMPHOID CELLS MEDIATING TUMOR-SPECIFIC CYTOTOXICITY TO CARCINOMA OF THE URINARY BLADDER
Authors: O'Toole C. , Stejskal V. , Perlmann P. , Karlsson M.
Published: June 2004

Peripheral lymphocytes from patients with urinary bladder carcinoma and controls have been separated on the basis of rosette formation with sheep erythrocytes. The fractions were tested for tumor-specific cytotoxicity. The E rosette-forming cells of purity ⩾ 90% respond well in PHA-induced cytotoxicity but are totally inactive in the tumor assay. The non-E rosette-forming cells (purity ⩾ 91%) give enhanced activity in the tumor-specific cytotoxicity as well as in antibody-mediated target cell lysis in a model system. These data support the notion that the effector cells in cell-mediated immunity to carcinoma of the urinary bladder are members of the nonthymus-derived population of peripheral lymphocytes.
THE ORIGIN OF CELL SURFACE IMMUNOGLOBULIN OF MARROW-DERIVED AND THYMUS-DERIVED LYMPHOCYTES OF THE RAT
Authors: Hunt Simon V. , Williams Alan F.
Published: June 2004

The origin of immunoglobulin on the surface of TDL in the rat has been studied by comparing the binding of purified alloantibodies recognizing the Ig-1a allotype of rat light chain, with that of rabbit antirat Fab antibodies. Both reagents labeled all TDL from rats of the DA strain (Ig-1a) with two categories of cells being detected; one binding 100–2,000 molecules of antibody, the other 10,000–100,000 molecules. These categories were likely to be synonomous with T and B cells, respectively. The [125I]antiallotype antibodies did not bind to TDL from rats of the PVG/c strain (Ig-1b).

When the binding to TDL from (PVG/c x DA)F1 animals was studied it was found that allelic exclusion occurred in the heavily labeled cells, but not in the lightly labeled ones. Furthermore, when lymphocytes of one allotype were transferred to irradiated recipients of the opposite allotype and recovered from the TDL or spleen of the recipient 20–30 h later, the immunoglobulin on heavily labeled cells was of the donor type, while that of lightly labeled ones bore the recipient marker. Thus heavily labeled cells (B lymphocytes) had synthesized their own immunoglobulin while lightly labeled cells (T lymphocytes) had acquired theirs passively by adsorption. The class of immunoglobulin on lightly labeled cells was also studied and it was found that [125I]anti-IgM antibodies bound to an extent approaching the [125I]anti-Fab binding, while [125I]anti-IgG2a+2b antibodies gave much less binding.
CONGENIC MOUSE STRAINS: THE EXPRESSION OF A HIDDEN IMMUNOGLOBULIN ALLOTYPE IN A CONGENIC PARTNER STRAIN OF BALB/c MICE
Authors: Bosma Melvin J. , Bosma Gayle C.
Published: June 2004

This paper derives from the unexpected observations of the "wrong immunoglobulin allotype" in a congenic partner strain of BALB/c mice from the Institute of Cancer Research (ICR CB-17). These mice were specially bred so as not to differ from BALB/c mice in any known way except to carry immunoglobulin structural genes of the C57BL/Ka allotype. In this respect, ICR CB-17 mice were defined as allotypically homozygous according to the Mendelian inheritance of mouse allotype markers. The homozygosity of these mice was challenged, however, when in certain instances immunoglobulins of the BALB/c allotype appeared in the serum of some ICR CB-17 mice. The appearance of this hidden allotype was usually transient and only associated with immunoglobulins of the IgG (IgG2a) class. The implications of these findings for the inheritance and expression of immunoglobulin structural genes are discussed.
FEEDBACK INHIBITION OF SPECIFICALLY SENSITIZED LYMPHOCYTES
Authors: Mackaness G. B. , Lagrange P. H. , Miller T. E. , Ishibashi T.
Published: June 2004

An explanation was sought for the fact that delayed-type hypersensitivity (DTH) does not normally occur in response to T-cell-dependent antigens unless an adjuvant is used. But when sheep red blood cells (SRBC) were administered intravenously DTH did appear, provided that the dose of antigen was less than that required to give a maximum antibody response. Animals in which T-cell activity had been blocked by a large dose of antigen could not be sensitized adoptively, and their spleen cells failed to transfer DTH to normal recipients. The serum of blocked animals partially inhibited the induction of DTH, and after absorption with SRBC its blocking activity increased substantially. Moreover, absorbed serum inhibited DTH in previously sensitized animals, but it did not inhibit the proliferative response to SRBC in peripheral lymph nodes or reduce the number of plaque-forming cells produced therein. On the contrary, the hemagglutinating titer was actually increased by blocking serum even though DTH was totally suppressed. It is concluded that a product of the interaction between antigens and antibody blocks the activated T cells which mediate DTH without interfering with helper cells.
ALLOANTISERUM-INDUCED INHIBITION OF IMMUNE RESPONSE GENE PRODUCT FUNCTION
Authors: Shevach Ethan M. , Green Ira , Paul William E.
Published: June 2004

It has been previously demonstrated that alloantisera can specifically block the activation of T lymphocytes by antigens, the response to which is linked to the presence of histocompatibility (H) types against which the alloantisera are directed. Thus, strain 13 anti-2 serum can inhibit the activation of (2 x 13)F1 T lymphocytes by a DNP derivative of a copolymer of L-glutamic acid and L-lysine (DNP-GL), an antigen the response to which is controlled by a 2-linked Ir gene. It was proposed that alloantisera can inhibit T-lymphocyte antigen recognition through interference with the activity of immune response (Ir) gene products. In order to further study whether the inhibitory antibodies within the alloantisera are directed against H antigens or against the products of the Ir genes, we have examined whether the anti-2 serum can inhibit the function of an Ir gene (the L-glutamic acid and L-alanine [GA] gene), which is normally linked to strain 2 H genes when this gene occurs in an outbred animal lacking strain 2 H genes. In the majority of cases, the anti-2 serum was capable of inhibiting the in vitro proliferative response to GA of T cells derived from animals that were GA+2+, but the serum had little if any effect on the GA response of T cells from GA+2- animals. Furthermore, an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2- outbred animal was devoid of inhibitory activity on the GA response of cells from a (2 x 13)F1, while an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2+ outbred animal was capable of specifically inhibiting the response to GA. It thus appears that the inhibition of the GA response by the anti-2 serum is primarily mediated via antibodies directed toward strain 2 H antigens rather than antibodies specific for the product of the GA Ir gene. The mechanism of alloantiserum induced suppression of Ir gene function would then be by steric interference with the Ir gene product on the cell surface, rather than by direct binding to it. This conclusion implies that the products of both the H genes and the Ir genes are physically related on the cell surface. The implications of such a relationship in terms of the fluid-mosaic model of the lymphocyte surface are discussed.
IMMUNOLOGICAL TOLERANCE
Authors: Shaw Andrew , Berko Barbara , Wegmann Thomas G.
Published: June 2004

Although most mouse strain combinations succumb to a lethal wasting disease when parabiosed across a strong histocompatibility (H-2) barrier, a high proportion of DBA mice parabiosed to DBA/C3H F1 hybrids survive and appear healthy. DBA mice accept C3H skin grafts following parabiosis, and may therefore be considered operationally tolerant of C3H antigens. Nonetheless, spleen cells from long-term DBA and F1 parabionts give normal and enhanced responses, respectively, to C3H antigens in mixed lymphocyte culture (MLC). This indicates that the tolerance mechanism can distinguish between MLC recognition reactivity and in vivo effector reactivity, and that the former can therefore exist in the absence of the latter.
RELATIONSHIP BETWEEN HL-A ANTIGENS AND ß2-MICROGLOBULIN AS STUDIED BY IMMUNOFLUORESCENCE ON THE LYMPHOCYTE MEMBRANE
Authors: Neauport-Sautes C. , Bismuth A. , Kourilsky F. M. , Manuel Y.
Published: June 2004

The antibody-induced redistribution of ß2-microglobulin (ß2-µ) and HL-A antigens on the surface of living lymphocytes was studied by immunofluorescence. When all ß2-µ was redistributed on the lymphocyte membrane by specific rabbit antibodies and goat antirabbit Ig conjugates, the HL-A antigens were no more detectable with anti-HL-A conjugates outside the ß2-µ caps already formed. However, the redistribution of HL-A antigens fails to provoke the redistribution of all detectable ß2-µ molecules. These results suggest that HL-A antigens may be associated with ß2-µ at the cell surface, but that all ß2-µ molecules are not bound to HL-A antigens.
ANTIBODY-INDUCED MOVEMENT OF MEMBRANE COMPONENTS OF LEISHMANIA ENRIETTII
Authors: Doyle John J. , Behin Reza , Mauel Jacques , Rowe David S.
Published: June 2004

Incubation in vitro of viable Leishmania enriettii with antibodies from infected or immune guinea pigs and a fluorescein-labeled antiguinea pig Ig conjugate induced aggregation of surface antigens to form a "cap" over the anterior pole of the amastigote and over both the anterior and posterior poles of the promastigote form of the parasite. Cap formation occurred only with optimum quantities of guinea pig antibodies and was inhibited by low temperature and the metabolic inhibitors, sodium azide and iodoacetamide. The aggregated antigens were rapidly lost from the surface of the parasite but reappeared after 3 h of incubation at 23°C. This phenomenon of ligand-induced membrane antigen movement is apparently similar to that described in mammalian cells, and may represent the first stage of the interaction between host antibodies and the surface membrane of protozoal parasites.
MECHANISMS OF GENETIC RESISTANCE TO FRIEND VIRUS LEUKEMIA IN MICE
Authors: Kumar Vinay , Bennett Michael , Eckner Robert J.
Published: June 2004

Resistance to malignant erythropoiesis induced by Friend spleen focus-forming virus and resistance to marrow stem cell allografts are under genetic control. Strains of mice, e.g., C57BL/6 and B10.D2, which are homozygous for resistance at the Fv-2 locus, are also good rejectors of most bone marrow allografts. 89Sr, a bone-seeking isotope, irradiates marrow but not other lymphoid organs and abrogates resistance to marrow allografts without suppressing T- or B-cell functions. Thus, marrow-dependent effector cells (M cells) seem to resist allogeneic stem cells. To test if the genetic resistance to Friend virus (FV) is also mediated by M cells, B6 mice were treated with 89Sr using a dosage schedule known to abrogate resistance to allogeneic marrow cells. 9 days after FV infection of such mice, the spleens showed malignant erythroblastosis which could not be suppressed by prior hypertransfusion, a procedure which suppresses physiologic erythropoiesis. Such 89Sr-treated B6 mice also supported extensive virus replication, while control mice did not. FV markedly suppressed the ability of 89Sr-treated B6 mice to produce antisheep red blood cell (SRBC) antibodies, a feature seen normally only in genetically susceptible mice. Thus, 89Sr-treated B6 mice behaved in these respects as if they were susceptible to FV. When increasing doses of 89Sr were administered to B6 mice, a dose-related loss of resistance to FV was seen. Therefore, it appears that 89Sr-sensitive M cells mediate the genetic resistance to FV.

The results of experiments with 89Sr indicated that genetically resistant mice would be expected to possess target cells which are susceptible to transformation by FV. To verify this corollary, bone marrow cells from B10.D2 (Fv-2rr) mice were transplanted into previously infected and lethally irradiated DBA/2 (Fv-2ss) recipients which share the same H-2d alleles. 5–15 days later, the spleens of DBA/2 primary recipients yielded transformed cells which were capable of producing splenic tumor colonies upon transplantation into adult, unirradiated B10.D2 secondary recipients. Various control experiments clearly indicated that the tumor colonies so induced were of B10.D2 marrow origin. This indicated that B10.D2 stem cells could be transformed when allowed to interact with FV in the spleens of susceptible DBA/2 mice. However, 30 days after transplantation of B10.D2 bone marrow cells into DBA/2 recipients, no transformed cells were detected. Apparently, in the 30-day interval precursors in the B10.D2 marrow gave rise to mature M cells which resisted the leukemic process. Since M cells recognize hybrid or hemopoietic histocompatability antigens expressed on primitive normal and transformed hematopoietic cells, we suggest that M cells may exert surveillance by rejecting leukemic cells. Thus, marrow transplantation from genetically resistant donors may provide a new mode of treatment for leukemia, by providing precursors of M cells and other immunocompetent cell types.
ONTOGENY OF B LYMPHOCYTES
Authors: Gelfand Michael C. , Elfenbein Gerald J. , Frank Michael M. , Paul William E.
Published: June 2004

Many bursa-equivalent (B) lymphocytes of adult mice bear surface Ig and receptors for C3. The frequency of Ig-bearing cells increases rapidly immediately after birth, but these cells lack complement (C) receptors. Lymphocytes bearing C receptors are not found in the spleens of BALB/c, DBA/2, and C57BL/6 mice until 2 wk of age and do not attain substantial numbers until 3–4 wk of age. In AKR mice, a lag between appearance of Ig-bearing and complement receptor lymphocytes (CRL) is also observed but it is of much shorter duration. AKR mice have a frequency of CRL at 2 wk of age of 28% in comparison to a frequency of 4.8% for DBA/2 mice. The difference in frequency between young and adult mice and between "low" and "high CRL" strains cannot be explained by a nonspecific inability to form rosettes as similar results are obtained with soluble antigen-antibody-complement complexes. Analysis of CRL frequency in (AKR x DBA/2)F1 mice and F1 x parental backcross progeny suggests that two independent genes control the rate of appearance of CRL. Furthermore, the genetic difference in the ontogeny of CRL is recapitulated in the repopulation of the B-lymphocyte line in adult-irradiated mice restored with syngeneic bone marrow. Thus, the "CRL genes" described here appear to control B-cell differentiation throughout life.
EFFECT OF NORMAL AND ACTIVATED HUMAN MACROPHAGES ON TOXOPLASMA GONDII
Authors: Anderson Seth E. , Remington Jack S.
Published: June 2004

Human macrophages derived from in vitro culture of peripheral blood monocytes were studied under a variety of conditions to determine their microbicidal capacity for the obligate intracellular protozoan, Toxoplasma gondii. The effect of macrophages on intracellular Toxoplasma was evaluated morphologically by light and phase microscopy and by autoradiography. When macrophages from dye test (DT)-negative or DT-positive individuals were infected with Toxoplasma in the presence of normal human serum, the organisms were able to multiply intracellularly with resultant destruction of the monolayer. Once organisms were intracellular, the presence of antibody-containing serum in the medium did not alter this inability of the macrophages to kill Toxoplasma. However, when Toxoplasma were incubated in the presence of heat-inactivated DT-positive serum just before infection of the monolayers, the intracellular organisms were inhibited or killed by normal macrophages. Attempts were made to activate macrophages in vitro to kill Toxoplasma. Macrophages incubated in the presence of sensitized lymphocytes and Streptokinase-Streptodornase (SK-SD) or Toxoplasma lysate antigen (TLA) were found to kill Toxoplasma when compared to macrophages incubated in the presence of lymphocytes from DT-negative individuals and TLA or lymphocytes alone. Thus, in vitro induction of resistance (both specifically and nonspecifically) in human macrophages was accomplished by culturing these cells in the presence of specifically sensitized lymphocytes and antigen. These results suggest that, as in the mouse model, activated human macrophages have the ability to inhibit or kill intracellular Toxoplasma and that these cells may be important as effector cells in cell-mediated immunity (CMI) to toxoplasmosis in man.
RECEPTORS FOR AGGREGATED IgG ON MOUSE LYMPHOCYTES
Authors: Anderson Clark L. , Grey Howard M.
Published: June 2004

An autoradiographic binding assay employing 125I-labeled heat-aggregated mouse IgG2b myeloma protein (MOPC 141) was used to demonstrate receptors for IgG on 20–45% of Balb/c thymocytes and on 70–80% of splenocytes. Binding could also be shown with heat or BDB aggregates of another IgG2b (MOPC 195), with IgG1 and with human γ-globulin, but not with aggregated chicken γ-globulin, IgA, BSA, nor with aggregated Fab fragments of IgG2b. Optimum binding was obtained at 37°C. Detection of binding was dependent upon aggregate size with complexes of more than 100 IgG molecules being optimal, aggregates of 6–25 detecting splenocytes but not thymocytes, and aggregates of less than 6 binding to a negligible extent. Comparison of grain counts on various cell types showed mastocytoma cells (P815) and macrophages averaging 40–50 grains/cell/day, allogeneically activated thymocytes 20–30, splenocytes 2–3, L5178 lymphoma cells 1, and positive thymocytes 0.6 grains/cell/day. Double labeling experiments for surface Ig, θ-antigen, and agg IgG receptor on mouse spleen cells indicated that a relatively high density of receptor was present on about 80% of B cells, 30% of T cells, and 60% of SIg-, θ-, null cells.
CHANGES IN CELLULAR ENZYME LEVELS AND EXTRACELLULAR RELEASE OF LYSOSOMAL ACID HYDROLASES IN MACROPHAGES EXPOSED TO GROUP A STREPTOCOCCAL CELL WALL SUBSTANCE
Authors: Davies Philip , Page Roy C. , Allison A. C.
Published: June 2004

Mouse peritoneal macrophages exposed to type-specific polysaccharide and peptidoglycan (PPG) from group A streptococci undergo marked morphologic and biochemical changes. The cells show increases in size and an increased number of lysosomes as demonstrated by vital staining with acridine orange. There are significant elevations in the levels of both lysosomal and nonlysosomal enzymes. Higher doses of PPG cause selective release of the hydrolases into the extracellular environment with no detectable loss of cell viability. The in vitro phenomena may be relevant to understanding the role of macrophages in chronic inflammation.
DEMONSTRATION AND CHARACTERIZATION OF TWO DISTINCT HUMAN LEUKOCYTIC PYROGENS
Authors: Dinarello Charles A. , Goldin Nathan P. , Wolff Sheldon M.
Published: June 2004

Human monocytes and neutrophils were separated from buffy coats of blood obtained from normal donors. Following incubation with heat-killed staphylococci, monocyte preparations contained 20 times more pyrogenic activity in the supernatant media than did supernates from an equal number of neutrophils. During purification of these pyrogens it was discovered that these cell preparations each produced a distinct and different pyrogen. The pyrogen obtained from neutrophils had a mol wt of 15,000 following Sephadex G-75 gel filtration, an isoelectric point of 6.9, and could be precipitated and recovered from 50% ethanol at –10°C. In contrast, the pyrogen derived from monocyte preparations had a mol wt of 38,000, an isoelectric point of 5.1, and was destroyed in cold ethanol. Both molecules were unaffected by viral neuraminidase but biologically destroyed at 80°C for 20 min and with trypsin at pH 8.0. The febrile peak produced by partially purified neutrophil pyrogen occurred at 40 min while that from monocytes was at 60 min. In addition, monocyte pyrogen produced more sustained fevers for the same peak elevation as neutrophil pyrogen. These studies demonstrate for the first time two chemically and biologically distinctive pyrogens derived from circulating human white blood cells and have important implications for our understanding of the pathogenesis of fever in man.
INDUCTION OF PARTIAL IMMUNOLOGIC TOLERANCE IN RATS AND PROGRESSIVE LOSS OF CELLULAR ANTIGENICITY IN GROSS VIRUS LYMPHOMA
Authors: Ioachim Harry L. , Keller Steven E. , Dorsett Brent H. , Pearse Antonia
Published: June 2004

Gross virus-induced lymphoma cells express strong virus-associated (Gross murine leukemia virus [G-MuLV]) antigens and are consistently rejected when grafted in normal adult syngeneic rats. By contrast, similar grafts are tolerated and allowed to grow progressively by rats that have been injected at birth with deaggregated G-MuLV antigens. However, the tolerance induced by this procedure is only partial as the grafted lymphoma cells lose their G-MuLV membrane antigens. These cells showing an antigenic disjunction, with negative membrane and positive cytoplasmic G-MuLV antigenic expression, become transplantable in normal-nonconditioned adult recipients. By further grafting, the expression of cytoplasmic G-MuLV antigens is similarly lost while the lymphoma cells substantially increase their transplantability, rate of growth, and capacity for metastasis.
IMMUNOLOGICAL TOLERANCE IN BONE MARROW-DERIVED LYMPHOCYTES
Authors: Katz David H. , Hamaoka Toshiyuki , Benacerraf Baruj
Published: June 2004

The present studies were designed to probe the role(s) of T cells in preventing or altering tolerance induction in hapten-specific B cells. This was accomplished by using hapten conjugates of normally immunogenic heterologous carriers to selectively inhibit 2,4-dinitrophenyl (DNP)-primed B cells in adoptive transfer experiments in vivo. The data provide strong indications that one critical role of T-cell participation in humoral responses to antigens is to circumvent the development of a tolerogenic signal that, in the absence of such T-cell function, might otherwise ensue after binding of the antigenic determinants by specific precursor B lymphocytes.
ANTIGENIC DIFFERENCES BETWEEN HEMOPOIETIC STEM CELLS AND MYELOID PROGENITORS
Authors: Van den Engh Gerrit J. , Golub Edward S.
Published: June 2004

Bone marrow contains pluripotent stem cells which give rise to colonies when injected into irradiated syngenic hosts as well as more differentiated progenitor cells of the myeloid cell which are able to form colonies in vitro. Antisera against brain is known to contain antistem cell antibody. The present experiments were designed to determine if the myeloid progenitor cell still expresses the stem cell antigen.

Bone marrow cells were treated with antibrain antiserum plus complement and then survival of stem cells was determined by injection into irradiated hosts. Survival of myeloid progenitor cells was determined by culturing the cells in vitro. It was found that stem cells were eliminated by the antiserum but that myeloid progenitors were not. Inefficient in vitro lysis was ruled out as the reason for this difference since in vitro colonies were not reduced when the cells were treated with anti-immunoglobulin or after passage through an irradiated host. In the differentiation from stem cell to myeloid progenitor there is an associated surface antigen change.
IMMUNE RESPONSES IN VITRO
Authors: Click Robert E.
Published: June 2004

The mixed leukocyte reaction stimulatory M-locus product of DBA/2 spleen cells was absent from thymus cells. The absence of stimulation was not a result of suppressor T cells. These findings are discussed in relation to the divergent specificity found for the inductive and effector phases of cell-mediated responses.
MUTANTS OF NONPRODUCER CELL LINES TRANSFORMED BY MURINE SARCOMA VIRUS
Authors: Tsuchida N. , Shih M. , Gilden R. V. , Hatanaka M.
Published: June 2004

BALB/3T3 cells transformed by the Kirsten sarcoma virus (nonvirus producer BALB/3T3 cells) and mutant cell lines derived therefrom by treatment with bromodeoxyuridine (BrdU) were analyzed for expression of virus-specific RNA using single-stranded DNA transcripts of Rauscher leukemia virus (RLV), a virus activated in one of the cell lines (58-2T), and Ki-SV-specific DNA transcript; the latter transcript after removal of all sequences cross-reactive with RLV RNA. The Rauscher virus DNA detected multiple copies of viral RNA in virus-producing cells (∼2.5 x 103/cell) whether infected with RLV or activated to produce virus with BrdU. Nonproducer (NP) cells and normal BALB cells showed small numbers of RNA genomes (70–250/cell) and only partial saturation of the transcript. The intracellular RNA sedimented at 35S (main peak) with a variable minor peak at 20S with the exception of one mutant cell, M-43-2 (main peak at 26–27S). The 58-2T transcript reacted preferentially in NP cells and their derivatives with biphasic kinetics suggesting the possibility of sequences specific for the original transforming virus. The size of Ki-SV specific sequences were 30S in mutant cells whether or not complete virus was being produced and independent of in vivo transplantability.
CELL INTERACTIONS BETWEEN HISTOINCOMPATIBLE T AND B LYMPHOCYTES
Authors: Katz David H. , Dorf Martin E. , Benacerraf Baruj
Published: June 2004

In our initial studies on the question of histocompatibility requirements in T-B-cell interactions, we found that no cooperation occurred with mixtures of T and B cells from BALB/c (H-2d) and A/J (H-2a) donors, respectively (1). These particular strains are identical for genes in the S and D regions of the H-2 complex but possess major differences at the K-end. Many differences are known to exist in the I region as well. Thus, these early data indicated that gene identities only at the D-end are insufficient to permit optimal cooperative interactions to occur under these conditions.
SYSTEMIC CELLULAR HYPERSENSITIVITY INDUCED BY AN INTESTINALLY ABSORBED ANTIGEN
Authors: Perrotto Joseph L. , Hang Le Ming , Isselbacher K. J. , Warren K. S.
Published: June 2004

Neonatal mice given intact living Schistosoma mansoni eggs or soluble schistosome egg antigens intragastrically developed systemic cellular hypersensitivity as shown by markedly accelerated, augmented granulomatous inflammation around S. mansoni eggs subsequently injected intravenously into the pulmonary microvasculature. To achieve partial sensitization in adult mice schistosome eggs had to be administered intragastrically with bicarbonate; full sensitization occurred when the eggs were injected intraduodenally. These data indicate that under appropriate conditions intestinal administration of antigen can result in systemic cellular immune sensitization.
THE IMMUNOLOGY OF EXPERIMENTAL CHAGAS' DISEASE
Authors: Santos-Buch Charles A. , Teixeira Antonio R. L.
Published: June 2004

Experiments that consisted of incubation of Trypanosoma cruzi-sensitized lymphocytes derived from chronically infected rabbits and from rabbits repeatedly immunized with a small particle or membrane fraction derived from homogenates of T. cruzi forms, showed destruction of allogeneic, parasitized and nonparasitized heart cells in vitro. Mononuclear cells collected from peripheral blood were incubated for 1 h at 37°C to isolate the lymphocytes. Following incubation, over 99% of the cells in the supernate were lymphocytes, which were utilized in these experiments. At the start of these experiments, 70–80% of the sensitized lymphocytes were unattached, small and round, with sparse filipodia. In the ensuing hours, marked heart cell destruction, similar to that seen in an active lesion when lymphocytes invade heart tissue, were observed. After 18 h incubation, about 65–70% of the lymphocytes were attached, larger, and rough surfaced.

Inhibition of monocyte migration tests, each in the presence of the antigens of subcellular fractions of T. cruzi organisms and of allogeneic heart myofibers, indicated the presence of a cross-reacting antigen common to both the parasite and the heart in the small particle or membrane fractions. The particulate antigens of the 30,000 g, 35-min fraction of heart muscle gave rise to inhibition of monocyte migration as did the counterpart fraction derived from T. cruzi organisms.

The destruction of nonparasitized target heart cells by T. cruzi-sensitized lymphocytes is an in vitro model of the chronic myocarditis of Chagas' disease, and the recognition of cross-reactive antigens of the host cell by T. cruzi-sensitized lymphocytes is believed to be the pathogenic basis for subsequent tissue injury in the chronic phase of this disease.
ROLE OF EXTRAPULMONARY CONVERSION IN MEDIATING THE SYSTEMIC PRESSOR ACTIVITY OF ANGIOTENSIN I
Authors: Oates Helen F. , Stokes Gordon S.
Published: June 2004

The effect of antibodies against angiotensin II (AII) on systemic pressor responses to intravenously injected AII and angiotensin I (AI) was studied in a group of bioassay rats. AII antibody was only 29% as effective in neutralizing AI given intravenously as it was in neutralizing AII injected by the same route. Control plasma caused no change in the relative potencies of AI and AII.

In a further series of experiments, AII antibody was significantly less effective in blocking intra-arterial AI than in blocking intravenous AI. The potency of intra-arterial AI, initially less than that of intravenous AI, became nearly twice that of intravenous AI after antibody administration, a result which could not occur if AI were inactive before lung transit. Thus, AI can elicit systemic pressor activity independently of pulmonary conversion to AII. However, since the intra-arterial AI responses were abolished by an inhibitor of angiotensin-converting enzyme, the activity would appear to be mediated by peripheral conversion to AII rather than by an intrinsic action of the decapeptide.

Both series of experiments suggest that the efficacy of AII antibody in abolishing the systemic pressor activity of AI is highly dependent on the site of conversion of the AI to AII. The occurrence of localized intramural conversion of AI to AII near arteriolar receptors in vivo may so minimize exposure of the liberated AII to circulating antibody as to render AII immunization an inefficient means of blocking endogenous pressor activity of the renin-angiotensin system.
CHARACTERISTICS OF IMMUNOLOGICAL MEMORY IN MICE
Authors: Black S. J. , Inchley C. J.
Published: June 2004

The kinetics of the generation of primed IgM and IgG antibody-forming cell precursors, and of helper T-cell populations, were analyzed in mice whose primary responses to high and low doses of SRBC were arrested at intervals by the immunosuppressive agents cyclophosphamide monohydrate and specific antibody. The extent to which immunological memory was established in these animals before blockade of the primary response was assessed by the hemolytic plaque assay following challenge 12 wk after priming. The presence of IgG B-memory cells and T-memory cells in suppressed mice was further investigated by the transfer into these animals of syngeneic SRBC-stimulated thymocytes or anti-θ-treated spleen cells.

It was found that the progenitors of secondary IgM-synthesizing cells were primed almost immediately after injection of antigen, and that early blockade of the primary response resulted in a raised IgM response after challenge. On the other hand, priming for a secondary IgG response took at least 4 days, and was dose-dependent, although helper T populations for a secondary IgG response appeared 3 days after antigen injection. It appeared that both IgM and IgG memory cells may be considered as Y cells in terms of the X-Y-Z scheme of lymphocyte activation, but that the two populations are generated at different times after exposure to antigen. The size of either Y-cell population at any given time is dependent upon the amount of antigen available to provoke differentiation to antibody-forming Z cells, and the IgM Y-cell population in particular is likely to be depleted during the course of a normal 1° response. When IgM Y cells were maintained for long periods as a result of immunosuppression, their secondary antibody response was independent of the primed T cells necessary for a secondary IgG response.