bluuebunny/crossref_metadata_2025 huggingface dataset:
Binding of components of the properdin system to cultured human lymphoblastoid cells and B lymphocytes.
Authors: Theofilopoulos A N , Perrin L H
Published: June 2004

Immunofluorescence studies showed that properdin (P) and factor B bind to C3-C3b receptor bearing human lymphoblastoid cells (Raji, Daudi) and B type human peripheral lymphocytes (HPL). P bound to Raji cells first incubated with normal human serum (NHS). EDTA, but not EGTA, halted the binding of P to cells incubated with NHS. However, fixation of P to Raji cells, after incubation with NHS first reacted with inulin, was independent of Ca++ and -g++ ions. Fixation of P to Raji cells depended on the presence of C3 or C3b and occurred in the absence of factor D and factor B. Binding of P to B type HPL was detectable only after incubation of these cells with NHS first reacted with inulin; under these conditions binding of P to Raji cells was also greatly enhanced. With both Raji cells and HPL, factor B was detectable on cell surfaces only after incubation of these cells with NHS first reacted with activators of the P system. Binding of factor B to cells required the presence of C3b and binding or stabilization of cell bound factor B necessitated the presence of activated P. P and factor B were detectable only on cultured cells having C3-C3b receptors. However, incubation of NHS with all lymphoblastoid cell lines studied resulted in activation of P and cleavage of factor B. Binding of P and factor B to cells may follow one of three sequences; (a) activated P in fluid phase combines with C3, factor D, and factor B, and the whole complex fixes to cellular C3-C3b receptors via its C3 moiety; (b) C3b generated in fluid phase combines with P, C3, factor D, and factor B and binds to C3-C3b receptors; or (c) C3 or C3b first binds onto the C3-C3b receptors and thereafter interacts with P, factor D, And factor B. Binding of components of the P system to cells or other particles may relate to such biological phenomena as lysis, phagocytosis, proliferation, attraction of other cell types, and alteration of responsiveness to external stimuli.
Antibody response of rabbit blood lymphocytes in vitro. Kinetics, clone size, and clonotype analysis in response to streptococcal group polysaccharide antigens.
Authors: Braun D G , Quintáns J , Luzzati A L , Lefkovits I , Read S E
Published: June 2004

Peripheral blood lymphocytes (PBL) of rabbits previously hyperimmunized against streptococcal groups A and A-variant antigens were stimulated in vitro by the corresponding vaccines to produce group-specific antibody. This response was dependent on an optimal cell density (2 X 10(6) cells/ml), on the presence of antigen, it was specific and cross-reactive due to a shared rhamnose backbone of the two polysaccharide antigens, and it was highly selective, such that in a 42-55-day culture 1 out of 20 viable cells was a specific PFC. During the exponential increase of the antibody concentration at a constant number of PFC, antibodies were secreted at a rate of 2.4 X 10(4) molecules/s per cell until a plateau level of antibody (40 mug/culture) was reached. The microculture system was used to determine the minimal frequency of group polysaccharide-specific precursor cells in the blood. Independent of the time elapsed since the last immunization this frequency was 1-3 X 10(-5), i.e., in the range of 1-2.8 X 10(2) precursor cells per ml blood. This number was further used together with the clonotype analysis of the culture supernates to calculate the frequencies of precursors of major and minor clonotypes. A hierachy of persisting clonal memory precursor cells was found indicating that clonal dominance is determined by locked-in frequency patterns and therefore it is a phenomenon based on numbers of cells that respond to the antigen.
Modification of murine T-cell cytotoxicity by preimmunization with M locus and H-2 incompatibilities.
Authors: Matossian-Rogers A , Festenstein H
Published: June 2004

The effect of preimmunization of CBA/H mice with M locus and H-2 incompatible lymphocytes was examined on the in vitro generation of cytotoxic cells to both types of targets. Preimmunization with M locus did not help to generate cytotoxic cells to M-locus targets; however, the anti-H-2 cytotoxicity of M-locus-preimmunized lymphocytes was suppressed between the 6th and 19th day after preimmunization. In contrast, preimmunization with H-2 incompatibility produced an amplified lytic anti-H-2 response. The possible mechanisms are discussed.
Regulation of the T-cell response to ectromelia virus infection. I. Feedback suppression by effector T cells.
Authors: Pang T , Blanden R V
Published: June 2004

Spleen cells and serum from mice immunized with ectromelia virus suppressed the immune response to infectious virus when transferred intravenously into recipient mice given an immunizing virus dose. The suppression was reflected in decreased cytotoxic T-cell activity directed against H-2 compatible virus-infected target cells in the spleens of recipients. Suppression was observed when immune cells or serum were transferred 1-2 h or 1 day after immunization of recipients, but not 2 days after, and was maximal when 6-day immune spleen cells were used as suppressor cells. H-2 compatibility between donor and recipient mice was necessary for suppression to be expressed. Use of recombinant mice showed that I-region compatibility was neither sufficient nor necessary, and that D-region compatibility was sufficient. Specificity of suppression was suggested by the finding that cells and serum from mice immunized with Listeria monocytogenes, a bacterium, had no suppressive activity on the antiviral response. Anti-theta treatment eliminated the ability of immune cells to suppress, and the suppressive effect was not markedly dose-dependent with respect to both cell dose and virus dose under the conditions employed. Virus levels in the spleens of recipients were significantly reduced after injection of immune cells. Adult thymectomy had no effect on the primary immune response to ectromelia virus infection, thus indicating no role for T1 cells in the suppressive mechanism. The results obtained therefore suggested that suppression in this system was due to effector T cells which triggered clearance of virus (and thus, of virus-induced antigens) necessary for the induction of precursors of effector T cells, and that this simple feed-back mechanism normally plays an important role in the regulation of the primary immune response to ectromelia infection at the level of precursor induction. The existence of other postinduction regulatory mechanisms, however, is unknown and under investigation.
Epithelial cell binding of group A streptococci by lipoteichoic acid on fimbriae denuded of M protein.
Authors: Beachey E H , Ofek I
Published: June 2004

Group A streptococci were treated with various enzymatic and chemical agents in an attempt to dissociate the type-specific M protein from intact surface "fimbriae." Mild peptic digestion at pH 5.8, which was previously shown to extract serologically active M antigen from intact streptococci had little visible effect on the fimbriae even though virtually all of the M protein was removed as demonstrated by (a) increased susceptibility to phagocytosis, (b) lack of opsonic effect of homologous M antibody on the treated streptococci, and (c) loss of HCl-extractable M protein. These fimbriated streptococci which lacked M protein adhered to human oral mucosal cells equally as well as untreated, fimbriated organisms which retained their M protein. Removal of both fimbriae and M protein by digesting organisms with HCL at pH 2.0 at 94 degrees C. or with trypsin abolished their ability to bind mucosal cells. Electron microscopy of streptococci bound to epithelial cells demonstrated fimbriae radiating from the surface of the organisms to the membrane of the epithelial cells. It is apparent, therefore, that the determinants of streptococcal fimbriae involved in resistance to phagocytosis can be dissociated from those involved in epithelial cell binding. These results are consistent with our previous studies which suggested that fatty acids ester linked with glycerol teichoic acid rather than M protein of streptococci binds the organisms to epithelial cells.
X-gp70: a third molecular species of the envelope protein gp70 of murine leukemia virus, expressed on mouse lymphoid cells.
Authors: Tung J S , Shen F W , Fleissner E , Boyse E A
Published: June 2004

Three variants of the gp70 envelope component of MuLV are now recognizable serologically: GIX-gp70, 0-gp70, and X-gp70. The last of these, X-gp70, has so far been found only in mice or cells producing abundant C-type virus. This distinguishes X-gp70, provisionally, from the GIX-gp70 and 0-gp70 variants, each of which can be expressed on normal thymocytes without accompanying virus production, as exemplified by mouse strains 129 and B6, respectively. The X-gp70 genotype, however, is not limited to strains of mice-producing abundant virus, because X-gp70+ leukemias occur in strains of mice which do not produce a great deal of virus and whose thymocytes and other tissues are X-gp70-; this is analogous to the appearance of GIX+ leukemias in GIX- mouse strains.
Hematopoietic thymocyte precursors. I. Assay and kinetics of the appearance of progeny.
Authors: Kadish J L , Basch R S
Published: June 2004

A quantitative assay for the hematopoietic precursor of thymocytes has been developed. Using this assay the kinetics of appearance of the progeny of transfused bone marrow and spleen cells in the thymus of irradiated (760 R) mice has been studied. Precursor cells are seven to eightfold more common in bone marrow than in spleen and are absent from peripheral lymph nodes. They decline in number as the animals age. When hematopoietic cells are injected immediately after lethal irradiation only a small number of cells actually enter the gland. Their progeny are not detectable in the thymus for 8-12 days. The time of their detection depends both upon the size of the residual endogenous thymocyte population and the number of progenitor cells injected. Evidence has been presented that excludes thymic injury as the basis for the delay in the appearance of donor type cells and indicates that neither the production of a "homing" signal in the irradiated animal nor the development of precursor cells are limiting factors in the rate of thymic repopulation. These studies indicate that only an exceedingly small number (less than 100) of prothymocytes are required to repopulate the thymus of an irradiated mouse. This restricted number of progenitors must produce the entire repertory of T-cell immunologic responsiveness seen in the first weeks after repopulation.
Alpha-fetoprotein synthesis by murine lymphoid cells in allogeneic reactions.
Authors: Keller R H , Tomasi T B
Published: June 2004

Surface-bound alpha-fetoprotein (AFP) was demonstrated by immunofluorescence on approximately 1/3 of splenic lymphocytes in chronic murine graft vs. host (GVH) reactions. Splenic lymphocytes were also shown to have a suppressed phytohemagglutinin (PHA) response compared to controls while lymph node cells from the same GVH animals revealed no surface AFP and had normal PHA responses. Splenic lymphocytes showed marked synthesis of AFP in the GVH and mixed lymphocyte culture (MLC) reactions by [14C]leucine incorporation and by radioimmunoassay in MLC supernates. Lymph node cells, however, demonstrated less synthetic activity and 14C counts in their membrane fractions were not markedly elevated.
Virus-induced diabetes mellitus. VI. Genetically determined host differences in the replicating of encephalomyocarditis virus in pancreatic beta cells.
Authors: Yoon J W , Notkins A L
Published: June 2004

Beta cells were isolated from strains of mice that were susceptible and resistant to encephalomyocarditis (EMC) viral-induced diabetes mellitus. Beta cells from susceptible mice that were infected in vivo with EMC virus showed higher viral titers, more severe degranulation, and lower concentrations of immunoreactive insulin than beta cells from resistant mice. Immunofluorescence and infectious center assays revealed that pancreas from susceptible mice contained at least 10 times more infected cells than pancreas from resistant mice. Beta cell cultures prepared from susceptible mice and infected in vitro also showed higher viral titers and more severe cytopathologic changes than beta cell cultures from resistant mice. In contrast to beta cell cultures, virus replicated equally well in primary embryo and kidney cell cultures from susceptible and resistant strains of mice. It is concluded that the development of EMC virus-induced diabetes is related to genetically determined host differences in the capacity of the virus to infect beta cells.
Characterization of DNA excreted from phytohemagglutinin-stimulated lymphocytes.
Authors: Rogers J C
Published: June 2004

The DNA released into the culture medium after phytohemagglutinin (PHA) stimulation of human peripheral blood lymphocytes has been purified and characterized. It is double stranded, sediments at 7-8S in alkaline sucrose, and has a Tm determined optically and by thermal elution from hydroxyapatite that is substantially lower than that found for lymphocyte cell DNA. Media DNA contains a major component reassociating with an average Cot-1/2 of 87 mol X s/liter, compared to a Cot-1/2 of 770 mol X s/liter for the unique fraction of cell DNA as measured by reassociation in 0.6 M Na+. This component of media DNA consists of unique sequence elements which are largely shared in media DNA preparations from cultures derived from different cell donors. The marked difference between media DNA and cell DNA indicates that media DNA is not derived from cell death and lysis, rather than some unique portion of lymphocyte DNA is apparently excreted from the cells during PHA-stimulated growth.
Growth of B-lymphocytes clones in semisolid culture is mitogen dependent.
Authors: Kincade P W , Ralph P , Moore M A
Published: June 2004

A substance which was mitogenic for murine B lymphocytes in the presence of 2-mercaptoethanol was isolated from agar. Stimulating activity of this material was stable to proteolysis or protein denaturants but was destroyed by periodate treatment. Agar-derived mitogen stimulation was distinct from that obtained with dextran sulfate or lipopolysaccharide and may define different populations of B lymphocytes.
The HLA system in the families of patients with juvenile diabetes mellitus.
Authors: Rubinstein P , Suciu-Foca N , Nicholson J F , Fotino M , Molinaro A , Harisiadis L , Hardy M A , Reemtsma K , Allen F H
Published: June 2004

The HLA and Bf genotypes were determined in 10 families with one or more children with JDM. A statistically significant association was found between HLA-D-identity and the chance to present JDM within a sibship. No such association was detectable with the SD antigens. A highly significant increase in the frequency of intra-HLA recombination was also found in these families.
Effect of recent antigen priming on adoptive immune responses. IV. Antigen-induced selective recruitment of recirculating lymphocytes to the spleen demonstrable with a microculture system.
Authors: Sprent J , Lefkovits I
Published: June 2004

When thoracic duct lymphocytes (TDL) from mice given sheep erythrocytes (SRC) 1 day previously (1-day-primed TDL) were placed in microcultures with antigen for 5-6 days, the cells failed to produce antibody to SRC, but responded well to horse erythrocytes (HRC); reciprocal results were obtained with TDL from HRC-injected mice. The specific unresponsiveness of the TDL was observed despite the presence of an allogeneic factor in the cultures; this factor exerted not only a macrophage-like effect (TDL from normal mice failed to respond in the absence of this factor) but also a T-cell-replacing function. It was concluded therefore that the unresponsiveness of the TDL was the result of selective recruitment of specific B lymphocyte precursors from the recirculating lymphocyte pool to the lymphoid tissues; whether there was also recruitment of specific T lymphocytes was not investigated. Since addition of 1-day-primed TDL to cultures of normal TDL did not inhibit the response of the latter, there was no evidence that active suppression accounted for the unresponsiveness. The spleen appeared to be the main site for recruitment since 1-day-primed spleen cells placed in microcultures contained above normal numbers of specifically-reactive precursors. This was in striking contrast to the effect of transferring 1-day-primed spleen cells in vivo where, as previously reported, the cells fail to respond to the injected antigen within 1 wk of transfer. An explanation for this paradox is discussed.
The requirement for membrane sialic acid in the stimulation of superoxide production during phagocytosis by human polymorphonuclear leukocytes.
Authors: Tsan M , McIntyre P A
Published: June 2004

The effect of desialylation on phagocytosis of latex particles and oxidative metabolism of human polymorphonuclear leukocytes was studied. Removal of 20% total leukocyte sialic acid by bacterial neuraminidase had no effect on phagocytosis of latex particles and phagocytosis-associated activation of hexose monophosphate shunt in human polymorphonuclear leukocytes. In contrast, desialylation prevented the stimulation of superoxide production either by phagocytosis or by concanavalin A. It is concluded that membrane sialic acid is essential for the stimulation of superoxide production by human polymorphonuclear leukocytes.
The behavior of skin grafts incompatible with respect to skin alloantigens on mice rendered tolerant at birth with lymphoid cells.
Authors: Silvers W K , Wachtel S S , Poole T W
Published: June 2004

It has been reported that lethally irradiated adult B6 mice restored with (A X B6) hemopoietic cells subsequently reject adult A-strain skin grafts because they are not tolerant of A-strain skin-specific (Sk) antigens. This thesis has been confirmed by a series of experiments conducted on neonatally treated animals. Thus sublethally irradiated neonatal B6 mice, inoculated with (A X B6) lymphoid cells, permanently accept these cells while subsequently rejecting adult strain A skin grafts. Further evidence that the destruction of these grafts results from the reaction of the host to Sk antigens, is provided by the fact that similarly treated recipients often permanently accept neonatal A-strain skin. Such grafts usually induce tolerance of adult A-strain skin grafts.
Cell interactions in the suppression of in vitro antibody responses.
Authors: Calkins C E , Orbach-Arbouys S , Stutman O , Gershon R K
Published: June 2004

Normal T and immune B lymphocytes interact in a fashion that leads to suppression of the immune response. Normal spleen cells added to cultures of primed spleen cells specifically suppressed both the IgM and IgG secondary antibody response of the primed cells to less than 30% of the response of the immune cells cultured alone. Cell crowding as a possible in vitro artifact was ruled out. The suppression was specific for the priming antigen, even when the specific and nonspecific antigens were included in the same cultures. Suppression required both normal T and immune B cells to be present in culture. We suggest that the immune population produces a signal that can induce normal T cells to become specific suppressor cells. This form of interaction may represent an important regulatory (homeostatic) mechanism in the immune system.
Transduction of bacteriocin determinants in group A streptococci.
Authors: Tagg J R , Skjold S , Wannamaker L W
Published: June 2004

Determinants of streptococcin A-FF22 (SA) production and host cell immunity have been transduced to three serologically distinct Group A streptococci. Streptomycin resistance markers were not cotransducible with bacteriocin determinants. SA+ transductants of strains unrelated to the parent SA+ strain were unstable but SA+ transductants of a spontaneous SA- derivative of the parent appeared to be stable.
Cellular basis of neonatal induction of in vitro tolerance.
Authors: Kuperman O J , Bach F H
Published: June 2004

The LD and SD antigens of the major histocompatibility complex subserve differential roles in the induction of the proliferative phase in mixed lymphocyte culture and in the cytotoxic reaction seen in cell-mediated lympholysis. The present study suggests that they also behave differently in the neonatal induction of tolerance. SD antigens appear to induce tolerance in the cytotoxic T lymphocytes very effectively, whereas LD antigens (or the cytotoxic targets coded by genes in the I and/or S regions) are relatively ineffective in this regard. LD antigens presented neonatally are effective at inducing tolerance in the proliferating helper cells.
Antibody response of C3H in equilibrium (CKB X CWB)F1 tetraparental mice to poly-L(Tyr,Glu)-poly-D,L-Ala-poly-L-Lys immunization.
Authors: Bechtol K B , McDevitt H O
Published: June 2004

To test whether the antigen-specific stimulation of low responder-genotype B cells in tetraparental mice is due to a histoincompatibility reaction (allogeneic effect) against these B cells, tetraparental mice were constructed (a) between an Ir-1A low responder to the antigen poly-L(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys. [(T,G)-A--L] and an Ir-1A F1 high responder and (b) between two histoincompatible Ir-lA low responders. In the first case the F1 high responder embryo shares the whole of the H-2 complex, including Ir, with the low responder embryo.
Histocompatibility antigens and genetic control of the immune response in guinea pigs. III. Specific inhibition of antigen-induced lymphocyte proliferation by strain-specific anti-idiotypic antibodies.
Authors: Geczy A F , Geczy C L , de Weck A L
Published: June 2004

The in vitro T-cell proliferation induced by penicilloylated bovine IgG (BPO-BGG) in sensitized strain 2 and strain 13 guinea pigs could be specifically blocked by strain-specific antisera presumably directed against cell membrane-associated immunoglobulin idiotypes. The anti-idiotypic antisera were prepared in strain 2 and strain 13 guinea pigs against immunoadsorbent purified anti-BPO-BGG antibodies which had been raised in strain 2 and strain 13 animals. Strain 13 antistrain 13 anti-BPO-BGG (a strain 13 BPO-BGG) suppressed the in vitro BPO-BGG response of cells from immunized strain 13 animals but did not inhibit the response of cells from immune strain 2 animals. Conversely, the corresponding antiserum raised in a strain 2 combination (a strain 2 BPO-BGG) only inhibited the in vitro BPO-BGG response of strain 2 cells. Furthermore, the inhibitory activity of the antisera could only be absorbed by immune cells from the syngeneic strain. The activity of the a strain 13 BPO-BGG serum was highly specific; the inhibitory activity could only be absorbed by BPO-BGG-sensitive strain 13 cells. The inhibitory activity of the anti-idiotypic sera was predominantly associated with the 19S fraction. The data suggest that immune cells and in particular T lymphocytes from strain 2 and strain 13 guinea pigs possess strain-specific recognition structures from BPO-BGG with the same idiotypes as the corresponding strain-specific immunoglobulins. Furthermore, the production of such inhibitory anti-idiotypic sera was restricted to syngeneic combinations, which suggests a potential role of autoanti-idiotypic antibodies in the regulation of the immune response. The anti-idiotypic antisera used here are apparently directed against gene products not associated with the strain 2 or strain 13 major histocompatibility complex.
Variation and control of specific antigen-binding cell populations in individual fetal mice.
Authors: D'Eustachio P , Cohen J E , Edelman G M
Published: June 2004

To determine the extent and nature of individual variation in the development of specific antigen-binding cells, the numbers of cells specific for each of two antigens in the spleens of individual random-bred Swiss-L and inbred CBA/J and BALB/c fetal mice were measured as a function of spleen size. For Swiss-L fetuses, the ratio of antigen-binding cells to nucleateated cells varied more than would arise from sampling fluctuation. For each inbred strain, however, the number of cells specific for a given antigen was a constant proportion of the total number of nucleated cells within sampling error. These proportions varied from antigen to antigen, and from strain to strain. The ratio of the proportions of cells specific for the two antigens, however, differed no more from CBA/J to BALB/c mice than would be expected in repeated samples of cells from the spleen of a single fetus. These results confirm at the level of the individual fetus the uniform pattern of development seen for populations of fetuses. They reveal a surprising precision in the proliferation of specific antigen-binding cell populations and suggest that the development of these cells may be subject to strong genetic controls.
Genetic regulation of the antibody response to H-2Db alloantigens in mice. II. Tolerance to non-H-2 determinants abolishes the antibody response to H-2Db in B10.A(5R) mice.
Authors: Wernet D , Lilly F
Published: June 2004

B10.A(5R) mice (H-2i5), immunized with spleen cells from congenic B10 mice (H-2b), responded to alloantigens of the H-2Db region by producing antibodies of only IgM type. In contrast, they produced both IgM and IgG antibodies when immunized with noncongenic H-2b cells that carry other foreign cell surface antigens (non-H-2) in addition to H-2Db. A hypothesis was proposed comparing the H-2Db antigen on a congenic cell to a hapten on a nonimmunogenic carrier which fails to induce T-cell helper function responsible for the switch from IgM to IgG secretion in B cells. Data presented here confirmed this hypothesis. 5R mice rendered tolerant to the relevant non-H-2 antigens were unable to mount the anti-H-2Db IgG response in a noncongenic immunization. Tolerance induction did not lead to abrogation of the T-cell mediated cytotoxicity.
Genetic control of specific immune suppression. III. Mapping of H-2 complex complementing genes controlling immune suppression by the random copolymer L-glutamic acid(50)-L-Tyrosine(50) (GT)
Authors: Debre P , Waltenbaugh C , Dorf M , Benacerraf B
Published: June 2004

Earlier studies from our laboratory demonstrated that the terpolymer of L-glutamic acid, L-alanine, and L-tyrpsine (GAT) stimulated the development of T cells capable of specifically suppressing the antibody responses in vivo and in vitro of nonresponder strains (bearing the H-2(s), H-2(q), and H-2(p) haplotypes) to GAT complexed with an immunogenic carrier, methylated bovine serum albumin, MBSA (1,2). We then extended these findings to another antigen, the copolymer of L-glutamic acid and L-tyrosine (GT). None of 19 inbred or congenic resistant mouse strains developed antibody responses to GT after immunization with this synthetic polypeptide in adjuvants. All the strains investigated, however, developed IgG plaque-forming cells (PFC) primary responses to GT complexed with MBSA (3). This permitted us to determine that: (a) preimmunization with GT suppressed the response to GT-MBSA in certain but not in all strains; (b) the suppression could be transferred by thymocytes and spleen cells from GT-primed animals; (c) the development of GT-specific suppressor cells is under dominant control of H-2- linked gene(s) which have been designated specific immune suppressor genes (Is genes); (d) the Is genes are antigen specific since GAT-MBSA responses are suppressed by GAT in strains carrying the H-2(q) haplotype, while GT-MBSA responses are not suppressed by the related polymer GT in these same strains (3,4).

The experiments reported in this study map the Is genes responsible for GT-specific suppression within the H-2 complex. The data indicate that the K and D loci are not concerned with GT-specific suppression, and that this phenomenon is controlled by complementing or interacting genes which map on either side of cross-over events between the IB and IC subregions.
Association between Ia antigens and the Fc receptors of certain T lymphocytes.
Authors: Dickler H B , Arbeit R D , Henkart P A , Sachs D H
Published: June 2004

The Fc receptors of thymic and splenic T lymphocytes were detected using indirect immunofluorescence and soluble antigen-antibody complexes. 10-20% of thymocytes and 40-50% of Thy-1-positive splenic lymphocytes bound antigen-complexed Ig. The binding to thymocytes was partially inhibited (45-74%) by antibodies against antigens determined by the I region of the H-2 complex, but not by antibodies against K- or D-region antigens or Thy-1 antigen. The inhibition did not require the Fc portion of the inhibiting antibody. These results provide evidence that Ia antigens and the Fc receptors of some T lymphocytes are associated, and that the populations of T cells which bear these moieties at least partially overlap.
Suppression of reaginic antibody (IgE) formation in mice by treatment with anti-mu antiserum.
Authors: Manning D D , Manning J K , Reed N D
Published: June 2004

Neonatally initiated injection of anti-mu antiserum in mice has been shown to suppress the formation of reaginic antibodies in response to infection with the intestinal nematode, Nippostrongylus brasiliensis. This observation supports the hypothesis that IgE-producing cells arise from IgM-bearing precursors.
The Fc receptor on thymus-derived lymphocytes. III. Mixed lymphocyte reactivity and cell-mediated lympholytic activity of Fc- and Fc+ T lymphocytes.
Authors: Stout R D , Waksal S D , Herzenberg L A
Published: June 2004

The involvement of Fc- and Fc+ T cells, separated on the fluorescence-activated cell sorter, in proliferative and cytotoxic responses to alloantigens was examined. The cytotoxic lymphocytes generated by in vivo exposure to allogeneic tumor cells were shown to express the Fc receptor. The proliferative responses to alloantigen exposure in mixed lymphocyte cultures was equivalent in intensity for unseparated T cells, the Fc+ T-cell fraction, and the Fc- T-cell fraction isolated from nonsensitized spleen cells. In contrast, the cytotoxic responses generated by the Fc- T-cell fraction (less than 1% Fc+) were much weaker than the cytotoxic responses generated by the Fc+ T-cell fraction (80-90% Fc+), and the responses of the Fc+ T-cell fraction were generally weaker than, or equal to the responses of unseparated T cells (Fc- T less than Fc+ T less than or equal to unseparated T). Mixtures of the Fc- and Fc+ T-cell fractions mounted stronger cytotoxic responses than the sum of the responses of either fraction alone. Examination of the Ly phenotypes of the synergizing populations revealed that the CL precursor activity (Ly-2+ T cells) resided in the Fc- T-cell population, and that the amplifier T-cell activity (Ly-1+ T cells) resided in the Fc+ T-cell population. The data are discussed in terms of T-cell heterogeneity, differentiation, and intercellular interaction.
Antifluorescein affinity columns. Isolation and immunocompetence of lymphocytes that bind fluoresceinated antigens in vivo or in vitro.
Authors: Scott D W
Published: June 2004

A new method for the isolation of specific immunocompetent lymphocytes has been described in which lymphocyte populations are exposed to fluoresceinated antigens (FLAGs) in vivo or in vitro, and the FLAG-binding cells retained on antifluorescein affinity columns. Specific cells are then eluted with an unrelated FL-labeled protein and shown to be fully immunocompetent. This methodology has been applied successfully in diverse antigenic systems including polymerized flagellin and TNP-specific B cells and alloantigen-reactive cytotoxic T lymphocytes. The method is rapid, inexpensive (requiring only antifluorescein beads), and can be applied to any antigens (or antibodies) in which a fluorescein group can be introduced.
Isolation and immunologic characterization of a human. B-lymphocyte-specific, cell surface antigen.
Authors: Humphreys R E , McCune J M , Chess L , Herrman H C , Malenka D J , Mann D L , Parham P , Schlossman S F , Strominger J L
Published: June 2004

In addition to HL-A antigens, another cell surface protein complex has been obtained from membranes of the human B-lymphoblast cell line IM-1. This complex which was solubilized with papain, consisted of polypeptides of 23,000 and 30,000 daltons (p23, 30). Rabbit antisera to this material precipitated from [35S]methionine-labeled detergent-solubilized cells, three proteins of 39,000, 34,000, and 29,000 daltons. These antisera were specifically cytotoxic for B lymphocytes of peripheral blood, for B-lymphoblast cell lines, and for EAC rosette receptor-positive surface Ig-negative (Null) lymphocytes. The p23,30 complex was not present on T lymphocytes, EAC rosette receptor-negative Null lymphocytes, or platelets. In addition, the p23,30 complex from several cell lines inhibited alloantisera from multiparous Amish women which had been shown to recognize non-HL-A, B-lymphocyte antigens. Some other properties of the anti-p23,30 sera antisera were described.
Genetic and cellular aspects of xenogeneic mixed leukocyte culture reaction.
Authors: Lindahl K F , Bach F H
Published: June 2004

The nature of the antigens stimulating xenogeneic lymphocytes was studied using "primed LD typing". Human lymphocytes were sensitized in vitro against mouse spleen cells and restimulated with spleen cells of mouse strains sharing non-H-2 antigens or various regions of H-2 with the initial stimulating strain. The largest thymidine uptake was caused by restimulation with cells from the specific primary stimulator or an H-2-identical strain. Species-specific antigens or strain-specific antigens carried in the C57BL/10 background account for less than 15% of the total stimulation; a non-H-2 antigen associated with the Mlsalpha genotype caused moderate restimulation, amounting to 25% of the average H-2 response. Within H-2, the strongest restimulation was caused by antigens controlled by the I-A subregion; the K and D regions caused moderate, the I-C and S regions very weak, and the I-B subregion no restimulation. Thus, the genetic control of antigens stimulating xenogeneic and allogeneic MLC responses requires T cells and adherent cells, but in the human-mouse MLC, both cell types must come from the human responder; the majority of the proliferating cells are T cells. It is suggested that allograft and xenograft reactions are fundamentally identical processes, and that the relative vigor of alloaggression may be explained by secondary potentiating mechanisms depending on species-specific interactions between aggressor and target cells.
Two stages of B-cell memory development with different T-cell requirements.
Authors: Okumura K , Metzler C M , Tsu T T , Herzenberg L A , Herzenberg L A
Published: June 2004

We present evidence here for two stages in B-memory cell development, the first of which is T independent and the second T dependent. For these studies, we use a new type of T-deficient mouse (allotype suppressed) which specifically lacks T-helper activity (Th) for a subset of memory B cells responsible for approximately 10% of the overall IgG antibody response. We have shown elsewhere that these mice (SJL X BALB/c hybrids suppressed for Ig-1b) lack Th capable of helping Ig-1b memory cells, although they have normal Th activity for all other IgG memory B cells. This selective Th deficiency allows study of the effects of T depletion on memory development and avidity maturation of one population of B cells under conditions where the bulk of the immune response in the animal is proceeding normally, thus obviating environmental problems due to secondary effects of T depletion. With this sytem, we show that after a single priming dose of 2,4-dinitrophenyl-keyhole limpet hemocyanin, the memory B-cell pool in suppressed and nonsuppressed donors is indistinguishable with respect to magnitude and avidity of the response for all IgG antibodies produced, including Ig-1b antibody, despite the fact that expression of Ig-1b memory cells is prevented in intact Ig-1b-suppressed mice by the absence of Th capbale of cooperating with these memory cells. We have shown elsewhere that virtually all of the Ig-1b memory is carried by Ig-1b bearing cells. In contrast with the lack of suppressor T-cell effect on initial Ig-1b memory cell development, our data show that continued Ig-1b memory development is selectively impaired in suppressed mice. When primed mice are boosted repeatedly with the priming antigen, the average avidity of most of the IgG memory cells increases over 100-fold while there is no avidity increase in the Ig-1b component. To explain these data, we suggest that the development of high avidity memory occurs in two stages. The first stage, which occurs as a result of primary antigenic exposure, is the creation of a pool of IgG-bearing memory cells with a relatively low average avidity for the antigen. The appearance of these first stage memory cells does not require help from (post-thymic) Th, although Th are required for the expression of these memory cells (antibody production). The second stage of B-memory development requires both further antigenic stimulation and B-memory cell interaction with competent Th. This is a continuing process in which the number of memory cells in the pool remains relatively constant but the average avidity of these cells increases with continued antigenic exposure.
In vitro studies on the T-lymphocyte population of human milk.
Authors: Parmely M J , Beer A E , Billingham R E
Published: June 2004

Human milk lymphocytes (ML) can be partially purified and propagated in vitro as a means of assessing their immunological function. When exposed to a variety of stimuli known to activate T lymphocytes, ML respond in a unique manner that indicates a selected population of immunocompetent cells. ML are hyporesponsive to to nonspecific mitogens and respond in a reduced manner to histocompatibility antigens on allogeneic cells. In most cases, they are completely unresponsive to C. albicans although blood lymphocytes from the same patients respond to the antigen. The Kl capsular antigen of E. coli induces significant proliferation in lymphocytes obtained from milk, but fails to stimulate blood lymphocytes. This dichotomy of reactivity does not appear to result from suppressive factors or cells in milk or insufficient adherent cell function. Rather it appears to reflect the accumulation of particular lymphocyte clones in the breast and the local nature of mammary tissue immunity at the T-lymphocyte level.
Regulation by the H-2 gene complex of macrophage-lymphoid cell interactions in secondary antibody responses in vitro.
Authors: Pierce C W , Kapp J A , Benacerraf B
Published: June 2004

The ability of antigen-bearing syngeneic and allogeneic peptone-induced peritoneal exudate macrophages to support development of primary and secondary antibody responses by murine lymphoid or spleen cells in vitro has been investigated. The antigen used was the terpolymer of L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT). Syngeneic and allogeneic macrophages supported development of comparable primary antibody responses to GAT, indicating that genetic restrictions do not limit efficient macrophage-lymphocyte interactions in primary responses. By contrast, immunized spleen or lymphoid cells developed secondary antibody responses preferentially when stimulated in vitro with GAT on macrophages syngeneic to the macrophages used to present GAT during in vivo immunization. Thus, genetic restrictions regulate efficient macrophage-lymphocyte interactions in secondary antibody responses. These restrictions have been demonstrated from 2 to 8 wk after a single immunization with limiting quantities of GAT and are controlled by the H-2 gene complex. The implications that immune lymphocytes selectively recognize and respond to antigen presented in the context of the macrophage membrane-antigen complex which sensitized the lymphocytes initially are considered.
T-Lymphocyte precursors. I. Synergy between precursor and mature T lymphocytes in the response to concanavalin A.
Authors: Cohen J J , Fairchild S S
Published: June 2004

When mouse bone marrow cells are mixed with cortisol-resistant thymocytes and stimulated in vitro with concanavalin A, the mitogenic response observed is much greater than additive, that is, it is synergistic. Between 94 and 96% of responding cells could be identified as T cells (Thy-1 positive) and of these, 79-100% derived from the cortisol-resistant thymocyte population, not from the bone marrow. Purified macrophages could not replace bone marrow; and marrow depleted of mature T or B cells worked as well as normal marrow. Thus, T and B cells and macrophages were ruled out as the synergizing cell of bone marrow. Nude spleen contained 10 times as many precursors of T cells as did nude marrow and was 10 times better at synergy with cortisol-resistant thymocytes. This implication of the pre-T cell as synergizer was supported by the finding that the synergistic activity of marrow was lost on preincubation, but maintained if the preincubation medium contained thymosin or cyclic AMP. Thus, the ability to enhance the response of relatively mature T cells to Con A is a property of pre-T cells. It is anticipated that this property will allow more detailed studies of T-cell precursor development in mice, and possibly in man.
Three HLA-D region antigens defined by primed LD typing.
Authors: Bach F H , Jarrett-Toth E , Benike C J , Sheehy M J , Sondel P M , Bach M L
Published: June 2004

We have recently described a new method, primed LD typing or PLT, for specific identification of HLA-D antigens. Highly discriminatory PLT cells have been developed which clearly differentiate between cells of individuals that restimulate strongly and those that restimulate weakly. Seven such discriminatory PLT cells have been used to define three antigens called PL1, PL2, and PL3; two more PLT cells may define antigen(s) PL4.
Status of blood group carbohydrate chains in ontogenesis and in oncogenesis.
Authors: Watanabe K , Hakomori S I
Published: June 2004

Blood group ABH determinants in human erythrocytes are carried by four kinds of glycolipid carbohydrate chains, differing in their structural complexity. They are Aa, Ab, Ac, and Ad for A variants, and H1, H2, H3, and H4 for H variants (Table I and Fig 1). Based on the surface labeling of A variants and on the reactivity of erythrocytes to antibodies directed against H3 and against its degradation products, it is concluded that complex variants of A or H determinants (Ac and Ad/or H3 and H4) are absent or significantly low in fetal erythrocytes (80-150 days after gestation) and in new born erythrocytes, whereas these complex structures are fully developed in adult erythrocytes. In contrast, A determinants linked to simpler carbohydrate chains (Aa, Ab variants) are fully developed before birth and do not show significant change after birth. The precursor of blood group carbohydrate chains seems to be abundant in fetal or newborn erythrocytes. This assumption is based on the higher reactivity of fetal or newborn erythrocytes to an antibody, which is directed against the precursor N-acetylglucosaminly beta1 leads to 3 galactosyl beta1 leads to 4 glucosylceramide than in adult erythorocytes. Reactions of glycolipids of gastrointestinal mucosa, with antibodies directed against H3 glycolipid and its degradation products, were compared to that of gastrointestinal tumors. The reaction to bela Glc NAc1 leads to 3 beta Gall leads to 4 Glc leads to ceramide (structure 4), which is the precursor of all blood group glycolipids, was consistently high in many cases of tumor glycolipid than that of normal glycolipid. This as well as other evidence supports a general concept that the process of ontogenesis of a blood group carbohydrate chain occurs as step-by-step elongation and arborization, and that blocking of such a development of a carbohydrate chain occurs in the process of oncogenesis.
Genetic regulation of the antibody response to H-2Db alloantigens in mice. III. Inhibition of the IgG Response to noncongenic cells by preimmunization with congenic cells.
Authors: Wernet D , Shafran H , Lilly F
Published: June 2004

When B10.A (5R) mice (H-12i5) are immunized with spleen cells from congenic B10 mice (H-12b), they respond to alloantigens of the H-2Db region by producing antibodies of only IgM type. In contrast, they produce both IgM and IgG antibodies when immunized with A.BY cells (H-2b) that carry other foreign cell surface antigens (non-H-2) in addition to H-2Db. Preimmunization of 5R mice with two injections of congenic cells leads to an H-2Db specific inhibition of the IgG response to a subsequent immunization with A.BY cells. It is concluded that congenic B10 cells fail to activate helper T cells which are necessary to induce the switch from IgM to IgG production. Instead T- or B-cell tolerance may be induced with prohibits the subsequent IgG response to A.BY cells, possibly by way of suppressor T cells which may act either on B cells directly or via helper T cells.
Endotoxin protein: a B-cell mitogen and polyclonal activator of C3H/HeJ lymphocytes.
Authors: Sultzer B M , Goodman G W
Published: June 2004

A cell wall protein that is ordinarily complexed to the lipopolysaccharide endotoxin in gram-negative bacteria has been separated by the use of aqueous phenol. The protein is active as a B-cell mitogen and polyclonal activator of murine lymphocytes including the C3H/HeJ strain which is a nonresponder to lipoplysaccharide or lipid A.
Membrane transport by murine lymphocytes. I. A rapid sampling technique as applied to the adenosine and thymidine systems.
Authors: Strauss P R , Sheehan J M , Kashket E R
Published: June 2004

We have developed a rapid sampling technique for animal cells in suspension for the purpose of measuring membrane transport in lymphocytes. The method involves rapid centrifugation of cells through a layer of silicone oil into perchloric acid after incubation periods as short as 4 s. Using this method we have described the uptake of thymidine and the uptake and transport systems of adenosine by murine bulk nonadherent spleen cells. The two uptake systems are markedly different. Adenosine was shown to be taken up by classical carrier-mediated diffusion, while thymidine was not. In addition we have explored the metabolism of the two nucleosides under the conditions we employed for measuring transport or uptake; Both nucleosides are phosphorylated extensively. We also investigated the uptake and metabolism of thymidine over a 2-h interval the standard time used to measure DNA synthesis in lymphocytes. Unless cells were separated from medium by centrifugation through oil before TCA addition, the TCA precipitable counts exceeded the total radioactive uptake. Hence the standard method for measuring thymidine utilization yields estimates under these conditions which can be as much as 100% too high.
Antibodies reacting with cytoplasm of subthalamic and caudate nuclei neurons in chorea and acute rheumatic fever.
Authors: Husby G , van de Rijn I , Zabriskie J B , Abdin Z H , Williams R C
Published: June 2004

46% of sera from 30 children with rheumatic chorea showed IgG antibody reacting with neuronal cytoplasm of human caudate and subthalamic nuclei. The antibody was also detected in 14% of 50 children with active rheumatic carditis. 55 normal control sera, as well as 148 sera from a broad variety of other disease states showed a low prevalence (1.8-4.0%) of positive reactions. In rheumatic chorea the presence of anti-neuronal antibody appeared to correlate with severity and duration of clinical attacks. Antibody reacting with neuronal cytoplasm was completely removed by absorption with Group A streptococcal membranes or with isolated human neurons from caudate nucleus. Partial absorption of antibody was also recorded using Group A cell wall preparations but not with Group A carbohydrate. No absorption of positive reactions was seen with streptococcal Group D membranes or cell walls. In rheumatic chorea, anti-neuronal antibody appeared to represent cross-reaction with antigens shared by Group A streptococcal membranes.