bluuebunny/crossref_metadata_2025 huggingface dataset:
Ly phenotype of cytotoxic T cells for syngeneic tumor.
Authors: Shiku H , Takahashi T , Bean M A , Old L J , Oettgen H F
Published: June 2004

Our present and previous findings may be summarized as follows: The phenotype of C57BL/6 (B6) cytotoxic cells for allogeneic target cells is Thy-1+, Ly-1- Ly-2/3+, MSLA+, and Ig-. the phenotype of B6 cytotoxic cells for syngeneic tumor cells is Thy-1+, Ly-1+, Ly-2/3+, MSLA+, and Ig-. The phenotype of B6 cytotoxic cells for syngeneic tumor cells is Thy-1+, Ly-1+, Ly-2/3+, MSLA+, AND Ig-. Thus, differences in Ly phenotype appear to be exhibited not only by cytotoxic T cells as opposed to helper T cells, but also within subcategories of cytotoxic T cells.
Cell-mediated lympholysis to H-2-matched target cells modified with a series of nitrophenyl compounds.
Authors: Rehn T G , Inman J K , Shearer G M
Published: June 2004

The specificity of C57BL/10 cytotoxic effector cells generated by in vitro sensitization with autologous spleen cells modified with a series of related nitrophenyl compounds was investigated. The failure of trinitrophenyl (TNP)-sensitized effector cells to lyse TNP-beta-alanylglycylglycyl(AGG)-modified target cells is presented as evidence contradicting the intimacy or dual receptor model or T-cell recognition in its simplest form. Data are also shown indicating that sensitization with N-(3-nitro-4-hydroxy-5-iodophenylacetyl)-AGG-modified stimulating cells generates noncross-reacting clones of cytotoxic effector cells.
Normal rabbit alveolar macrophages. I. The phagocytosis of tubular myelin.
Authors: Nichols B A
Published: June 2004

Normal rabbit alveolar macrophages are engorged with large, dense inclusions which contain whorls of myelin figures, suggesting an exogenous source of polar lipids in their diet. One contributory source of such lipids is surfactant, since macrophages were seen ingesting tubular myelin and vacuoles containing remnants of it were found in the cytoplasm. Thus, as indicated previously in kinetic studies, it appears that alveolar macrophages participate in the turnover of surfactant. However, the relative importance of the macrophage in comparison to other pathways of surfactant removal remains to be determined. It is also noteworthy that although tubular myelin and myelin figures were abundant in the fixative used to wash out the lungs, bacteria were not found in it or in the macrophages. Thus, removal of obsolete surfactant may prove to be one of the mojor endocytic functions of alveolar macrophages.
Normal rabbit alveolar macrophages. II. Their primary and secondary lysosomes as revealed by electron microscopy and cytochemistry.
Authors: Nichols B A
Published: June 2004

In this investigation, vacuoles containing tubular myelin proved to be digestive compartments with cytochemical reactivity for acid phosphatase and arylsulfatase. These cytochemical markers identify the secondary lysosomes, known to contain enzymes capable of hydrolyzing phospholipids like surfactant. Therefore, it appears that alveolar macrophages possess the enzymatic machinery for the degradation of the tubular myelin found in their digestive vacuoles. Although it thus appears evident that alveolar macrophages participate in the turnover of surfactant, the quantitative significance of this route of disposal is undetermined. This investigation has also established that acid hydrolases, so prominently displayed in the secondary lysosomes, are also localized in the rough endoplasmic reticulum and in Golgi-endoplasmic reticulum-lysosomes (GERL). Moreover, small vesicles which are produced from GERL serve as primary lysosomes in transporting digestive enzymes to the vacuoles.
The analysis of the monoclonal immune response to influenza virus. II. The antigenicity of the viral hemagglutinin.
Authors: Gerhard W
Published: June 2004

The antigenicity of the hemagglutinins (HA) of five influenza viruses of the A0 and A1 subtypes has been analyzed by means of monoclonal antibodies of murine origin produced in vitro. Secondary monoclonal anti-HA(PR8) antibodies were able to differentiate 14 antigenic determinants (or groups of determinants) on the HA of five influenza virus strains of the A0 and A1 subtypes. Taking into account that certain pairs of determinants delineated on heterologous HA may reflect the heterogeneity of the humoral immune response to a single homologous determinant, the presence of at least eight determinants (host cell-derived determinants not included) on the homologous HA of PR8 and probably on the HA of influenza viruses in general is postulated. Three types of HA-determinants of A0 and A1 influenza virus strains could be distinguished: strain-specific, partially shared, and determinant(s) common to all five virus strains tested. Roughly 40, 55, and 5%, respectively, of the secondary anti-PR8 antibodies of BALB/c mice were directed against determinants belonging to either of the three types.
Modulation of the alternative complement pathways by beta 1 H globulin.
Authors: Whaley K , Ruddy S
Published: June 2004

C3b inactivator accelerator (A-C3bINA) was isolated from human plasma. An antiserum produced against the purified protein gave a reaction of identity with beta 1 H, a well-documented contaminant of C3 preparations. Beta 1 H appears to be composed of a single polypeptide chain containing a significant quantity of carbohydrate, and having a sedimentation coefficient of 5.6 on analytical, and 6.4 on sucrose density gradient ultracentrifugation. Its mol wt based on SDS polyacrylamide gel electrophoresis and equilibrium sedimentation is approximately 150,000, whereas it elutes from Sephadex G200 with an apparent mol wt of 300,000, suggesting that beta 1 H is an asymmetric molecule. Beta 1 H potentiates the inactivation of C3b by C3b inactivator, binds to EAC43 to limit the formation of EAC43bB and EAC43bBP, and in contrast to C3b inactivator, it increases the rate of loss of hemolytic sites from EAC43bB and EAC43bBP. For the C3b inactivator-potentiating effect, beta 1 H and C3b inactivator must necessarily be simultaneously present. The kinetics of inactivation of C3b by C3b inactivator and beta 1 H are first order, suggesting that potentiation is not a multistep process. The mechanisms of binding to C3b and inhibition of the alternative pathway convertases C3bB and C3bBP are currently unknown.
Genetics of the idotype of BALB/c myeloma S117: multiple chromosomal loci for Vh genes encoding specificity for group A streptococcal carbohydrate.
Authors: Berek C , Taylor B A , Eichmann K
Published: June 2004

A small proportion of the antibodies to Group A streptococcal carbohydrate (A-CHO) elicited in BALB/c mice by immunization with Group A streptococci, has idiotypic determinants in common with the BALB/c myeloma protein S117 which has specificity for N-acetyl-glucosamine, the major antigenic determinant of A-CHO. The expression of these idiotypic determinants is under the control of a gene which is linked to the Ig-1a+ allotype locus in strain BALB/c and in other strains carrying the same Ig-1 haplotype. This gene (S117+) segregates in breeding experiments as if it were an allele to the gene A5A+ which controls the expression of the A5A idiotype in association with antibodies to A-CHO in strain A/J and which is linked to the Ig-1e allotype locus. Another possible allele, linked to the Ig-1c allotype locus, controls the expression of both S117 and A5A cross-reactive determinants (S117cr, A5Acr). The distribution of these idiotypic determinants in various lines that carry recombinant Ig-1 haplotypes suggests that the A5A and S117 loci are nonallelic and map at different positions in the Ig-1 region. The data suggest complex pseudollelic relationships between different Ig-1 haplotypes that allow the expression of the same genes in allelic and in nonallelic fashion.
The chemotactic attraction of human fibroblasts to a lymphocyte-derived factor.
Authors: Postlethwaite A E , Snyderman R , Kang A H
Published: June 2004

A quantitative assay that measures fibroblast chemotaxis in vitro is described. Application of this technique has revealed that peripheral blood lymphocytes stimulated by antigen or mitogen in vitro produce a factor that is chemotactic for human dermal fibroblasts. This lymphocyte-derived chemotactic factor for fibroblasts (LDCF-F) is different from the lymphokine that is chemotactic for monocytes or macrophages. Macrophages are required for the generation of LDCF-F by T lymphocytes stimulated by phytohemagglutinin. The fibroblast chemotactic factor is heat stable (56 degrees C for 30 min), trypsin sensitive, and neuraminidase resistant. LDCF-F could function to attact connective tissue fibroblasts to sites at which cell-mediated immune reactions are occurring in vivo.
Isoantiserum-augmented development of lymphocyte-mediated cytotoxicity.
Authors: Faanes R , Walker M , Choi Y S
Published: June 2004

Passive administration of anti-P-814 isoantiserum (IS) with P-815 mastocytoma was shown to augment the development of T-lymphocyte-mediated cytotoxicity (LMC). The LMC activity augmented by IS was specific to immunizing tumor cells, but required the simultaneous administration of P-815 tumor cells and anti-P-815 serum, suggesting that the antigen-antibody complex is involved in the development of specific cytotoxic T cells. The serum component responsible for augmented development of LMC activity appeared to be IgM in that the augmenting activity fractionated in the void volume of a G-200 Sephadex column and appears very early after immunization. Our experimental results suggest the development of specific T-cell cytotoxicity can be directly regulated by specific IgM antibodies.
Reaginic antibody produced in mice with contact sensitivity.
Authors: Thomas W R , Asherson G L , Watkins M C
Published: June 2004

Mice produced reaginic antibody within 1 wk of painting with the contact sensitizing agent picryl chloride. The titers, measured by passive cutaneous anaphylaxis in rats, increased after repeated applications of picryl chloride. In contrast, serum agglutinins did not increase after two applications of picryl chloride. Reagin was also elicited by another contact sensitizing agent, oxazolone. Some strain variation of the response to picryl chloride was found, with CBA mice being good responders and BALB/c and C57BL/10 mice being poor responders.
Induction and abrogation of unresponsiveness in nude mouse cells.
Authors: Bösing-Schneider R , Haug M
Published: June 2004

Nude mice were injected with antigen and T cells at different times to induce unresponsiveness to SRBC. Spleen cells derived from these mice were tested in vitro for the capability to produce antibody-forming cells against sheep erythrocytes in the presence of a T-cell-replacing factor. It was found that priming with antigen alone did not result in paralysis but a later injection of thymus-derived lymphocytes together with antigen results in unresponsiveness of these cells in vitro, provided there was an interval of several days between the in vivo administration of thymus lymphocytes and the explantations of cells to in vitro cultures.
Identification of a subpopulation of lymphocytes in human peripheral blood cytotoxic to autologous fibroblasts.
Authors: Parkman R , Rosen F S
Published: June 2004

A naturally occurring subpopulation of human peripheral blood lymphocytes is cytotoxic to autologous and/or allogeneic fibroblasts. The autocytotoxic lymphocytes have a receptor for the third component of complement and for aggregated gamma globulin, do not form rosettes with sheep red blood cells, and are not removed by passage through nylon. The autocytotoxic subpopulation is not present in the thymus and tonsils of normal children or in the peripheral blood of individuals with X-linked agammaglobulinemia. Fibroblast absorption experiments demonstrate that the autocytotoxic cells are "sensitized" to antigens expressed on allogeneic fibroblasts in addition to the antigens expressed on autologous cells. Some normal individuals have a second subpopulation of lymphocytes that may "regulate" the autocytotoxic cells. The relevance of these observations to the murine autocytotoxic cells is discussed.
5'-Nucleotidase activity of mouse peritoneal macrophages. I. Synthesis and degradation in resident and inflammatory populations.
Authors: Edelson P J , Cohn Z A
Published: June 2004

Mouse resident peritoneal macrophages display sufficient 5'-nucleotidase activity to hydrolyze 58 nm AMP/min per cell protein. This activity increases approximately 163 nm AMP/min per mg after 72 h in culture. The enzyme is renewed in unstimulated cells with a half-time of 13.9 h. The activity is not reduced by treatment of intact cells with a variety of proteolytic enzymes, including trypsin, pronase, urokinase, and plasmin. Cells obtained from an inflammatory exudate have diminished or absent levels of enzyme activity. Endotoxin-elicited cells display enzyme activitiy of 20.9 nm AMP/min per mg, while thioglycollate-stimulated macrophages have no detectable activity. The reduced level of activity in endotoxin-stimulated cells is due to their elevated rate of enzyme degradation, with a half-time of 6.9 h. Their rate of enzyme synthesis is essentially normal. No evidence for latent enzyme activity could be obtained in thioglycollate-stimulated cells, nor do these cells produce any inhibition of normal cell enzyme activity. Serum deprivation reduces the enzyme activity of resident cells to about 45% of control activity. These conditions do not significantly affect the rate of enzyme synthesis, but again are explainable by an increase in the rate of enzyme degradation. Pinocytic rate is elevated in endotoxin-stimulated cells which show a more rapid rate of enzyme degradation than unstimulated cells do. However, in serum-free conditions, the rate of enzyme degradation is doubled with no change in the pinocytic rate of the cells.
The specificity of cellular immune responses II. The structure of antigenic determinants leading to T-lymphocyte stimulation.
Authors: Janeway C A , Maurer P H , Dailey M O , Inman J K
Published: June 2004

T cells from guinea pigs immunized with the hapten 2,4-dinitrophenyl (DNP)-coupled directly to mycobacteria are of interest since they recognize and respond to DNP conjugated to many but not all carriers. The experiments reported here further analyze the structure of the complex, chemically defined antigenic determinants recognized by such T cells. These antigenic determinants can have DNP coupled either to the xi-amino group of lysyl residues or to the hydroxyl group of tyrosyl residues. Furthermore, essential contributions to the determinant recognized by such T cells are made by amino acid residues to which the hapten is not attached. Such residues are thought to be close to the hapten group itself, since introducing a small spacer between hapten and carrier prevents recognition. The hapten itself is also recognized and discriminated from other haptens with great precision by these T lymphocytes. The strain of guinea pig immunized affects the precise specificity characteristics of the responding T cells, in a way that may reflect the activity of histocompatibility-linked immune response genes. Finally, the characteristics of the immunogen have been studied. It is thought that the lipid content of the mycobacteria may be critical in inducing the hapten-reactive T cells, and this is supported by finding similar responses in T cells from guinea pigs immunized with DNP protein to which lipid has been covalently attached. Thus, the T-cell population being studied, while recognizing haptens with great precision, appears to require a larger determinant for activation than do hapten-specific B lymphocytes.
Genetic control of the immune response to staphylococcal nuclease. IV. H-2-linked control of the relative proportions of antibodies produced to different determinants of native nuclease.
Authors: Berzofsky J A , Schechter A N , Shearer G M , Sachs D H
Published: June 2004

The relative proportions of antibodies of different specificities within antisera raised to native staphylococcal nuclease have been studied in several strains of mice in which the antibody response has been shown to be under H-2-linked Ir-gene control. A method was developed in which binding to different radiolabeled fragments of nuclease was titrated against increasing fragment concentration until the binding capacity of the antiserum for that fragment was saturated. In comparing the low responder (H-2b) strain C57BL/10 with its congenic high responder counterpart B10.A (H-2a), it was found that the two strains made markedly and reproducibly different proportions of antibodies to different determinants on native nuclease. Since these two strains differ only at H-2, and therefore have identical immunoglobulin structural gene repertoires, we conclude that H-2-linked Ir genes can control the response to different determinants on the same antigen molecule independently of one another. This result suggests a possible role of H-2-linked genes in the selection of specific B cells.
The in vitro effects of Bordetella pertussis lymphocytosis-promoting factor on murine lymphocytes: II. Nature of the responding cells.
Authors: Kong A S , Morse S I
Published: June 2004

The mitogenic response of murine lymphocytes to the lymphocytosis-promoting factor of Bordetella pertussis has been shown to be due to activation of T cells. The selectivity of responsiveness to LPF with respect to the population of T cells which is stimllated, differs from that of PHA as well as Con A, and the surface receptors are different. A population of adherent cells, which does not appear to consist of macrophages or other phagocytic cells, is required for the T-cell response.
A murine tumor producing a matrix of basement membrane.
Authors: Orkin R W , Gehron P , McGoodwin E B , Martin G R , Valentine T , Swarm R
Published: June 2004

We have studied a murine tumor previously classified as a poorly differentiated chondrosarcoma. Although the cells in this tumor are surrounded by large quantities of extracellular matrix material, the matrix fails to react with stains specific for the sulfated glycosaminoglycans present in normal cartilage. Here we show at the ultrastructural level that the tumor matrix is a homogeneous, nonfibrillar material, resembling basement membrane. Neither the proteoglycan matrix granules nor collagen fibrils characteristic of cartilage are present in the tumor matrix. Amino acid analyses of whole tumor tissue, enzyme-solubilized tumor components, and the protein extracted from lathyritic tumors confirmed that the tumor matrix is a basement membrane collagen. The collagenous protein extracted from the tumor by nonenzymatic means contains three unique polypeptides larger than the alpha-chain components of the other types of collagen. These studies indicate that the tumor is not a type of chondrosarcoma but a basement membrane producing tumor.
Characterization of self-reactive B cells by polyclonal B-cell activators.
Authors: Primi D , Hammarström L , Smith C I , Möller G
Published: June 2004

The existence of autoreactive B cells was predicted by theoretical considerations and, recently, confirmed by direct experiments. The aim of the present work was to investigate if the capacity of self-reactive B cells to be activated with different polyclonal B-cell activators (PBA) reflects the heterogeneity of the response as seen in all the Ig-positive cells. We injected mice with dextran sulfate, lipopolysaccharide from Escherichia coli 055:B5, and purified protein derivate of turbercle bacteria RT32 and studied the complement-dependent cytotoxicity against syngeneic spleen cells caused by the sera from injected mice with regard to the different parameters used for characterization of B-cell subpopulations. It was found that the capacity of self-reactive B cells to secrete antibodies reflects the polyclonal-activating capacity of the PBA used. The implications of these findings for the understanding of the triggering mechanism of B lymphocytes and for self-nonself discrimination are discussed.
The adjuvant effect of Corynebacterium parvum: T-cell dependence of macrophage activation.
Authors: Sljivić V S , Watson S R
Published: June 2004

Splenic and peritoneal macrophages from mice treated with Corynebacterium parvum enhanced the antibody response in vitro of normal nonadherent spleen cells to SRBC, but not to DNP-POL. This enhancement was dependent on the dose and time of administration of C. parvum and could be abrogated by pretreatment with carrageenan. Macrophages from T-cell-depleted mice failed to enhance the response, but this ability was restored if the mice had been reconstituted with purified T lymphocytes. Macrophages that are activated by C. parvum are a resident nondividing population. It is postulated that activated macrophages, capable of enhancing antibody responses to T-cell-dependent antigens, arise through a cell-mediated reaction to C. parvum.
Defective colony formation by B lymphocytes from CBA/N and C3H/HeJ mice.
Authors: Kincade P W
Published: June 2004

B cells from CBA/N mice did not form colonies in semisolid agar cultures under circumstances where normal B-cell clonal proliferation is linear with respect to the number of functional cells cultured. This was no due to the unresponsiveness of CBA/N cells to mitogens, and under appropriate liquid culture conditions many CBA/N lymphocytes differentiated to plasma cells containing large amounts of IgM in response to LPS. On the other hand, the same cells proliferated and matured poorly in liquid cultures prepared at low-cell density. The frequency of granulocyte-macrophage progenitors and multipotential hemopoietic stem cells in bone marrow, ability of peritoneal macrophages to elaborate soluble enhancing factors, and levels of serum inhibitors were normal in CBA/N mice. Together with the results of cell-mixing experiments, these findings confirm the selective and intrinsic nature of the CBA/N deficiency. It is suggested that the B-cell cloning technique may be of value in selectively enumerating and assessing functional capability of thymus-independent B cells. C3H/HeJ mice which have previously only been known to be hyporesponsive to certain forms of lipopolysaccharide had a subnormal incidence of colony-forming B cells.
Complement-mediated antiserum cytotoxic reactions to human chromosome 7 coded antigen(s): immunoselection of rearranged human chromosome 7 in human-mouse somatic cell hybrids.
Authors: Knowles B B , Solter D , Trinchieri G , Maloney K M , Ford S R , Aden D P
Published: June 2004

Immunoselection via complement-dependent lysis of human-mouse somatic cell hybrids containing chromosome 7, with antisera reactive to cell surface antigen(s) coded for by chromosome 7, has resulted in growth of somatic cell hybrids containing rearranged human chromosome 7s. Investigation of these hybrids has localized the gene(s) coding for the relevant cell surface antigen(s) to the short arm of human chromosome 7. The simian virus 40 integration site and the gene coding for human beta-glucuronidase appear to be localized to the long arm of chromosome 7 in this hybrid clone.
Histocompatibility antigens controlled by the I region of the murine H-2 complex. II. K/D region compatibility is not required for I-region cell-mediated lymphocytotoxicity.
Authors: Klein J , Chiang C L , Hauptfeld V
Published: June 2004

In the cell-mediated lymphocytotoxicity assay, A.TH effector cells sensitized to A.TL lymphocytes lyse not only A.B10.AQR effector cells lyse B10.BR and B10.BYR target cells in addition to B10.AQR cells. These findings indicate that for CML to occur across the IA region barrier, compatibility at K or D regions is not required.
Nonspecific activation of murine lymphocytes. I. Proliferation and polyclonal activation induced by 2-mercaptoethanol and alpha-thioglycerol.
Authors: Goodman M G , Weigle W O
Published: June 2004

The effect of 2-mercaptoethanol (2-ME) and alpha-thioglycerol (alpha TG) on proliferation and polyclonal activation of lymphocytes was studied in cultures of spleen cells from C3H mice. Inclusion in serum-free or serum-containing medium of the optimal concentration (5 x 10(-5) M) of either 2-ME or alpha TG resulted in highly significant uptake and incorporation of tritiated thymidine ([3H]TdR) into DNA and in morphological blast transformation. These phenomena were dose-dependent, with both lower and higher doses causing less marked effects. The kinetic peak of these responses was found to occur at day 3 of culture. Improved cellular viability could not explain these results, because by day 3 there was no significant difference in viability between cells cultured in the presence or absence of 2-ME. 2-ME evoked a proliferative response in cultures of congenitally athymic (nu/nu) spleen cells that exhibited a similar but lower dose-response profile compared with that of heterozygous (nu/+) littermates. Cultures of bone marrow-derived (B) lymphocytes, generated by treatment of spleen cells with rabbit antithymocyte serum and complement, incorporated [3H]TdR to a degree at least equal to that of normal spleen cell cultures. Thymus-dependent (T) cells did not support significant 2-ME, alpha TG, or Concanavalin A responses in the absence of serum. However, when cultured in 5% fetal calf serum, definite T-cell responses occurred, though always of a lower magnitude than B-cell responses in this system. When the enriched B-cell and T-cell preparations were co-cultured, a synergistic response was noted. Macrophage dependency of the 2-ME and alpha TG effect was shown to be minimal. It is likely that the greater effectiveness of alpha TG relative to 2-ME is due to differences in the chemical structure of these two thiol compounds. The advantages of utilizing 2-ME and alpha TG as probes in the study of lymphocyte activation are evaluated and their possible mechanisms of action are discussed.
Joint recognition by cytotoxic T cells of inactivated Sendai virus and products of the major histocompatibility complex.
Authors: Schrader J W , Edelman G M
Published: June 2004

Cytotoxic T cells specific for Sendai virus were generated by culturing murine spleen cells in vitro together with UV-inactivated Sendai virus. In vivo immunization of donor mice with UV-inactivated Sendai virus resulted in an in vitro secondary response of increased magnitude. Cytotoxic activity was demonstrated in a short-term 51Cr-release assay, using syngeneic tumor cells which had been coated with inactivated Sendai virus by incubation at 4 degrees C for 30 min. The lysis of Sendai virus-coated target cells was restricted by the H-2 haplotype of the target cells, suggesting that the H-2 genes of the target cell contributed to the specificity of the lysis. Kinetic experiments showed that susceptibility to lysis by cytotoxic T cells specific for Sendai virus appeared within 30 min after coating target cells with inactivated virus. Furthermore, there was no detectable synthesis of new proteins in cells treated with UV-inactivated Sendai virus. For these reasons, we suggest that neither viral replication nor the synthesis of new proteins are necessary for the production of the antigen recognized by cytotoxic cells specific for Sendai virus. We infer that the virus-specific component on the target cells is probably a preformed virion antigen adsorbed onto or integrated into the cell membrane. These results imply that, if the cytotoxic T cell recognizes a single antigenic determinant specified both by viral and H-2 genes, this determinant is formed by the physical association of H-2 and Sendai virus antigens rather than by their alteration during the processes of synthesis.
Frequency of occurrence of idiotypes associated with anti-p-azophenylarsonate antibodies arising in mice immunologically suppressed with respect to a cross-reactive idiotype.
Authors: Ju S , Gray A , Nisonoff A
Published: June 2004

Inoculation of rabbit anti-idiotypic (anti-id) antibodies suppresses the subsequent appearance of a cross-reactive idiotype (CRI) associated with the anti-p-azophenylarsonate (anti-Ar) antibodies of A/J mice. Such suppressed mice produce normal concentrations of anti-Ar antibodies which lack the CRI, but against which anti-id antisera can be prepared. The anti-Ar antibodies of an individual, suppressed mouse do not in general share idiotype with anti-Ar antibodies of other A/J mice, either suppressed or nonsuppressed. The present experiments were undertaken to quantitate several "private idiotypes" in a large number of hyperimmunized A/J mice. Anti-Ar antibodies of three mice, suppressed for the CRI, were labeled with 125I and subjected to isoelectric focusing. Four single peaks, that were over 90% reactive with autologous antiid, were randomly selected for use as ligands in a radioimmunoassay, and ascitic fluids containing anti-Ar antibodies from 181 A/J mice were tested as inhibitors. Two of the four idiotypes could not be detected in any mouse other than the donor. The concentration of the idiotype was less than 1 part in 1,250 to less than 1 part in 25,000 of the anti-Ar antibody population; these are minimum values. A third idiotype was detected in 3 of the 181 mice, but at very low concentrations. The fourth idiotype was present in 28% of the mice, again at a low concentration. The data support the existence of a very large repertoire of anti-Ar antibodies in the A/J strain and are consistent with a process of random somatic mutation for generating diversity in hypervariable regions. It is proposed that the cross-reactive idiotype may be controlled by a germ line gene or a gene related to a germ line gene through a small number of somatic mutations; and that the idiotypes that were not detectable in other mice were the products of genes that had undergone extensive mutations, with a low probability of recurrence in other mice.
Generation of both cross-reactive and virus-specific T-cell populations after immunization with serologically distinct influenza A viruses.
Authors: Effros R B , Doherty P C , Gerhard W , Bennink J
Published: June 2004

Specificity of cytotoxic T-cell function was investigated for a range of different influenza viruses. T cells from mice immunized with A or B strain influenza viruses, or with vaccinia virus, showed reciprocal exclusion of cytotoxicity. Extensive cross-reactivity was, however, found for lymphocyte populations from mice infected with a variety of serologically distinct influenza A viruses, though serum antibodies did not cross-react when tested in a radioimmunoassay using comparable target cells as immunoadsorbents. This apparent lack of T-cell specificity was recognized for immune spleen cells generated after intraperitoneal inoculation of high titers of virus, and for mediastinal lymph node populations from mice with pneumonia due to infection with much less virus. The phenomenon could not be explained on the basis of exposure to the chicken host component, which is common to A and B strain viruses. However, not all of the virus-immune T-cell clones are cross-reactive. Competitive-inhibition experiments indicate that a considerable proportion of the lymphocyte response is restricted to the immunizing virus. Even so, the less specific component is significant. Also, exposure to one type A virus was found to prime for an enhanced cell-mediated immunity response after challenge with a second, serologically different A strain virus.
Genetic control of the immune response to nuclease. V. Genetic linkage and strain distribution of anti-nuclease idiotypes.
Authors: Fathman C G , Pisetsky D S , Sachs D H
Published: June 2004

Rat antisera raised against anti-nuclease antibodies from mouse strains A/J and SJL detect strain-specific idiotypic determinants related to the antigen-combining site. These antisera have been used to investigate the genetic linkage and strain distribution of the anti-nuclease idiotypes. Despite the existence of an H-2-linked immune response gene controlling the humoral response to nuclease, expression of the A/J anti-nuclease idiotype has been shown to be independent of genes in the H-2 region: the A/J idiotype was present in immune sera from strains A/J (H-2a) and A.BY (H-2b) but absent in sera from strains B10 (H-2b) and B10.A (H-2a). An analysis of the segregation of the A/J idiotype in offspring of the backcross (A/J x B10.A) x B10.A demonstrated linkage to the Ig-1e heavy chain allotype markers. In a small sample of backcross animals a very high apparent recombination frequency was observed, but further backcross analyses and progeny testing of putative recombinant animals will be required to substantiate this observation. Analysis of the A/J and SJL anti-nuclease idiotype markers in the BALB/c, CB.20, and BAB.14 strains indicate that these idiotypic markers may permit mapping of distinct variable region genes.
Independent populations of primed F1 guinea pig T lymphocytes respond to antigen-pulsed parental peritoneal exudate cells.
Authors: Paul W E , Shevach E M , Pickeral S , Thomas D W , Rosenthal A S
Published: June 2004

Thymus-dependent (T) lymphocytes from (2 x 13)F1 hybrid guinea pigs immunized to ovalbumin (OVA) in complete Freund's adjuvant can be stimulated to proliferate in vitro by antigen-pulsed peritoneal exudate cells (PECs) derived from either strain 2 or strain 13 donors. In this communication, we show that the population of primed F1 T lymphocytes which can be activated by antigen-pulsed strain 2 PECs is largely independent of the population of cells that can be activated by antigen-pulsed strain 13 PECs. This was demonstrated by both positive and negative selection procedures. In the former, T lymphocytes from OVA-primed (2 x 13)F1 donors were enriched by initial culture with OVA-pulsed strain 2 or strain 13 PECs for 1 wk. Cells selected by culture with OVA-pulsed strain 2 PECs responded well to OVA-pulsed strain 2 PECs and poorly to OVA-pulsed strain 13 PECs. If positive selection had been carried out with OVA-pulsed strain 13 PECs, the selected F1 T cells responded well to OVA-pulsed 13 PECs and poorly to OVA-pulsed 2 PECs. Negative selection was achieved by short term culture with antigen-pulsed PECs and by eliminating proliferating cells by treatment with bromodeoxyuridine and light. This procedure demonstrated that the population of primed F1 T lymphocytes which are responsive to OVA or to purified protein derivative of tuberculin can be divided into subpopulations uniquely responsive to antigen on either strain 2 or strain 13 PECs. Evidence was presented to indicate that this selective responsiveness was not the result of the action of alloantigen-specific suppressor cells. The results are considered in terms of current concepts of the genetic and molecular regulation of the interaction of PECs and T lymphocytes.
Immune response gene control of determinant selection. I. Intramolecular mapping of the immunogenic sites on insulin recognized by guinea pig T and B cells.
Authors: Barcinski M A , Rosenthal A S
Published: June 2004

T-cell DNA synthesis and T-helper cell function in response to isolated insulin chains and naturally occurring insulin variants was assessed in insulin immune guinea pigs. Two distinct antigenic determinants, recognized by T cells, were defined. One localized in the B chain and the other one constituted by amino acids A8, A9, and A10 of the insulin A-chain loop. Recognition of the B-chain determinant is under the control of Ir genes linked to the strain 13 major histocompatibility complex. This was shown by studying the response to isolated insulin B chain in F1(2 x 13) guinea pigs, as well as serologically defined backcrosses and outbred animals. Insulin recognition through the A-chain loop determinant is specific for strain 2 guinea pigs. These animals recognize this region of the molecule even when displaying different amino acid sequences. The strain differences observed in those antigenic sites eliciting T-cell recognition was not found at an antibody level. No differences could be detected in the ability of the different insulin variants to inhibit the binding of 125I-labeled pork insulin to strain 2 guinea pig anti-pork insulin or to strain 13 guinea pig anti-pork insulin.
Prevention of IgG2a production as a result of allotype-specific interaction between T and B cells.
Authors: Bosma M J , Bosma G C
Published: June 2004

BALB/c T cells, which can prevent normal C57BL IgG2a allotype (G2) production of Ig-congenic partner mice (C.B mice), are shown capable of preventing the growth and G2 production of a C.B plasmacytoma (CBPC 101). Such cytotoxic or suppressor T cells are clearly allotype-specific (G2 Tcs cells). And since CBPC 101 B cells do not require specific helper T cells in order to grow, we infer that G2-bearing B cells (normal or neoplastic) must be the direct target of G2 Tcs cells. This mode of T cell prevention of allotype production contrasts that reported for suppressor T cells in (BALB/c x SJL)F1 mice.
DNA-binding property of Sm nuclear antigen.
Authors: Reyes P A , Tan E M
Published: June 2004

Antibodies in the sera of patients with systemic lupus erythematosus reacted with a nuclear acidic protein called Sm antigen, and these antibodies were used as reagents to identify Sm antigen in preparative fractionation procedures. DNA affinity chromatography showed that Sm antigen was associated with nuclear protein fractions which had DNA-binding capacity. Evidence was also presented that Sm antigen showed preferential binding for single-strand DNA over double-strand DNA. These studies demonstrate that spontaneously occurring anti-nuclear antibodies in disease states may be used to study the properties of cellular proteins which are present in trace amounts.
Eosinophils and resistance to Trichinella spiralis.
Authors: Grove D I , Mahmoud A A , Warren K S
Published: June 2004

Mice infected with Trichinella spiralis were depleted of eosinophils by repeated administration of rabbit anti-mouse eosinophil serum. There was no effect on the spontaneous expulsion of adult worms from the small intestines, but the numbers of larvae in the muscles were almost doubled. It is concluded that eosinophils contribute to resistance to the systemic phase of trichinosis.
Parallel synthesis of immunoglobulins and J chain in pokeweed mitogen-stimulated normal cells and in lymphoblastoid cell lines.
Authors: Mestecky J , Winchester R J , Hoffman T , Kunkel H G
Published: June 2004

The synthesis of intracellular J chains was found to be closely associated with that of intracellular immunoglobulin, regardless of its class, during the process of B-cell differentiation. This parallelism between the synthesis of J chain and immunoglobulin was particularly evident in their coincident appearance in serial observations of pokeweed mitogen (PWM)-stimulated lymphocytes. The intensity of J-chain staining by fluorescent reagents in the stimulated cells synthesizing IgG was similar to that found in cells synthesizing IgA or IgM. Evidence was obtained that the presence of J chain in the IgG-producing cells did not reflect antecedent synthesis of IgA or IgM. T cells stimulated by phytohemagglutinin and PWM failed to show J-chain synthesis. Observations on lymphoid cell lines showed a similar parallelism between intracellular Ig and J-chain synthesis; no relation to surface Ig was found.
Ia antigenic specificities are oligosaccharide in nature: hapten-inhibition studies.
Authors: McKenzie I F , Clarke A , Parish C R
Published: June 2004

We have previously reported that the Ia specificities, coded for by the I region within the H-2 complex, appear to consist predominantly of carbohydrate. This conclusion was reached by examining low molecular weight Ia-bearing oligosacharides isolated from mouse serum. We now report hapten-inhibition studies which indicate that the binding of both allogeneic and xenogeneic anti-Ia antibodies to the Ia glycoproteins found predominantly on B lymphocytes can be specifically inhibited by certain free sugars. Both inhibition assays revealed that the specificity for the following Ia antigens resides predominantly in the following sugars: (a) Ia.1: N-acetyl-D-mannosamine or related sugars; (b) Ia.3: alpha-D-galactose and related sugars; (c) Ia.7: L-fucose; and (d) Ia.15: N-acetyl-D-glucosamine. It seems likely that these sugars are found at the terminal nonreducing ends of the carbohydrate portion of the Ia-bearing glycoproteins present in the lymphocyte membrane. In contrast, several public and private H-2 antigenic specificities did not appear to be sugar defined. These studies imply that at least some of the Ia genes from both the I-A and I-C subregions of the I region code for glycosyl transferases which modify oligosaccharide structure and impart specificity to the Ia antigens by alteration of their terminal sugar residues.
Molecular similarities between the Qa-2 alloantigen and other gene products of the 17th chromosome of the mouse.
Authors: Michaelson J , Flaherty L , Vitetta E , Poulik M D
Published: June 2004

The alloantigen Qa-2, whose gene is located on the 17th chromosome between H-2D and Tla, is identified as a molecule of 43,000 daltons which is associated with beta 2-microglobulin. Qa-2 comprises approximately 0.15% of the iodinateable cell surface protein of lymph node cells. Sequential precipitations demonstrated that Qa-2 is distinct from H-2D and H-2K molecules.
Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis.
Authors: McWilliams M , Phillips-Quagliata J M , Lamm M E
Published: June 2004

The fate of mesenteric lymph node lymphoblasts labeled with either [125I]iododeoxyuridine or [3H]thymidine can be studied after intravenous transfer into syngeneic mice both by measurement of radioactivity in various organs and by combined immunofluorescence and autoradiography of recipient tissues. Many of the lymphoblasts home to the lamina propria of the small intestine within hours of transfer; of these, many visibly secrete IgA. To determine whether the cells that will ultimately secrete IgA are already committed to IgA synthesis before their arrival in the gut, mesenteric lymph node cell populations were treated with various class-specific antisera to mouse immunoglobulins before transfer. Treatment with antiserum to IgA, plus complement, reduced the fraction of injected label recovered from the recipients' intestines, and also reduced the proportion of donor (labeled) cells containing IgA. We conclude that mesenteric lymph nodes are probably the principal source of IgA-secreting plasma cells in the lamina propria of the gut, and that the cells become committed to IgA synthesis and develop cell surface IgA before emigrating. This IgA is apparently synthesized by the cells that bear it since it is not removed by extensive rinsing at 37 degrees C, a maneuver that elutes passively adsorbed immunoglobulin.
Differences in the mechanism of tolerance to dinitrophenylated bovine gamma globulin when induced in normal adult mice or in reconstituted irradiated mice: dependence of the mechanism of tolerance on the structural organization of the lymphoid system.
Authors: Szewczuk M R , Halliday M , Soybel T W , Turner D , Siskind G W , Weksler M E
Published: June 2004

Tolerance can be induced in adult mice by a single intravenous injection of 0.5 mg dinitrophenylated bovine gamma globulin. The cellular mechanism of the unresponsive state is different depending upon whether the tolerance is induced in normal intact adult mice or in reconstituted, irradiated mice. The tolerant state induced in intact mice is characterized by a high avidity of the residual antibody-forming cells in partially tolerant animals and a prompt reversibility on cell transfer. The overall properties of this unresponsive state are consistent with the hypothesis that it is mediated by the production of small amounts of high affinity antibody in response to the tolerance-inducing injection of antigen. In contrast, the unresponsiveness induced in reconstituted, irradiated mice by the same procedure was characterized by a low avidity of the residual antibody-forming cells in partially tolerant animals and stability on transfer of spleen cells from unresponsive into irradiated recipients. No suppressor cell activity was detected and mixed cell transfer studies were consitent with the view that this unresponsive state represented a B-lymphocyte clonal deletion. The presence or absence of T lymphocytes in the population of cells used for reconstituting the irradiated recipients did not effect the ease of tolernace induction or the cellular mechanism of the tolerant state which was produced. If irradiated mice reconstituted with B and T lymphocytes were rested for 2 wk before tolerance induction then a reversible "high affinity"-type tolerance is obtained such as is typical of normal intact animals. Restorationof a "normal" response to the tolerance-inducing injection of antigen is dependent upon the presence of thymus cells in the population of cells used for reconstitution. It is suggested that the structural integrity of the lymphoid tissue is critical in determining whether B cell will be rendered tolerant after exposure to antigen in vivo.
Features of systemic lupus erythematosus in mice injected with bacterial lipopolysaccharides: identificantion of circulating DNA and renal localization of DNA-anti-DNA complexes.
Authors: Izui S , Lambert P H , Fournié G J , Türler H , Miescher P A
Published: June 2004

After injection of lipopolysaccharides (LPS) in mice, there is first a release of DNA into plasma and secondly an induction of anti-DNA antibodies. The circulating DNA was purified from plasma and physico-immunochemically characterized. This DNA has a similar density to mammalian cellular DNA,is 4--6S insize, and probably represents a mixture of single-stranded DNA (SSDNA) and double-stranded DNA (DSDNA) or DSDNA with some single-stranded regions. This purified DNA was shown to react with anti-DNA antibodies which appeared as early as 3 days after a single injection of LPS in mice. In serum, DNA-anti-DNA complexes were not detected, although unidentified circulating immune complex-like material was demonstrated 5-8 days after the injection of LPS. In tissues, particularly in renal glomeruli, fine granular immune complex-type immunoglobulin deposits appeared along the glomerular capillary walls and in the mesangium 3 days after the injection of LPS. There is a direct correlation between the level of anti-DNA antibodies and the intensity of glomerular deposits and about 40% of immunoglobulins eluted from kidneys are anti-DNA antibodies, indicating that some of the immune complexes localized in kidneys are DNA-anti-DNA complexes. Based on these observations, the following hypothetical mechanism for the glomerular localization of DNA-anti-DNA complexes after the injection of LPS in mice is proposed. First, DNA, which has been released in circulating blood after injection of LPS, might bind to renal glomeruli, probably on glomerular basement membranes (GBM) through a high affinity of GBM for DNA; secondly, circulating anti-DNA antibodies, which appear later, might react with the glomerular-bound DNA and form immune complexes independently of circulating immune complexes. However, the possibility of direct deposition of immune complexes is not ruled out.