bluuebunny/crossref_metadata_2025 huggingface dataset:
Antibody-specific immunoregulation
Authors: Pierce SK , Klinman NR
Published: June 2004

In recent years, much evidence has accumulated which demonstrates that an animal's immune system has the capacity to recognize its own antibody idiotypes. These findings suggest that self-idiotypic recognition may potentially play a role in the regulation of B-cell responses. The experiments presented in this report were carried out to determine if an animal develops the ability to specifically regulate the synthesis of antibodies specific for an antigen, subsequent to primary immunization to the particular antigen and concomitant with an initial antibody response. Employing the splenic fragment culture system we have compared the response of primary donor B cells in irradiated recipients which have been previously immunized to hemocyanin (Hy) alone or dinitrophenyl (DNP)-Hy plus Hy. The results indicated that only 25-30 percent of DNP- specific B cells stimulated by DNP-Hy in Hy immunized recipients could bestimulated by DNP-Hy in recipients immunized with Hy as well as DNP-Hy. B-cell responses to other haptens, such as fluoresceinated-Hy, and secondary DNP-specific B-cell responses were unaffected in DNP-Hy immunized animals. The nontrivial and specific nature of the observed decrease in primary DNP-specific B-cell responses was verified by the finding that the response of CB20 donor cells, which differ from BALB/c mice only in the immunoglobulin heavy chain allotype-linked locus, was unaffected in BALB/c recipient mice which had been immunized with DNP-Hy. Thus, it appeared that during a primary humoral immune response to a T- dependent antigen, an antibody-specific regulatory mechanism is induced which specifically limits the stimulation of hapten-specific primary, but not secondary, B cells. The important implications that these findings have for the understanding of the control of primary B-cell responses and the generation of secondary B cells is discussed.
The guinea pig I region. II. Functional analysis.
Authors: Shevach E M , Lundquist M L , Geczy A F , Schwartz B D
Published: June 2004

We have examined whether an association exists between specific Ia antigen genes and Ir genes which are encoded within the same haplotype. Functionally monospecific sera to the Ia antigens of the guinea pig MHC were selective in their ability to inhibit antigen-specific T-cell proliferation and we were thus able to demonstrate an association between individual Ia specificities and specific Ir genes. The results of these studies in inbred animals were confirmed by examining the association of Ir genes and Ia antigens in the outbred guinea pig population. Of great interest was the observation that antisera made against cross-reactive Ia antigens of strains lacking specific Ir genes would still inhibit immune responses of strains possessing the Ir gene, if the Ir gene was associated with that Ia antigen in the responder strain.
Coupled complementation of immune response genes controlling responsiveness to the H-2.2 alloantigen.
Authors: Dorf M E , Stimpfling J H
Published: June 2004

The ability of various B10 congenic resistant strains to respond to the alloantigen H-2.2 was tested. High and low antibody-producing strains were distinguished by their anti-H-2.2 hemagglutinating respones. However, these strains do not differ in their ability to respond to these antigenic differences in the mixed lymphocyte culture. The humoral response to the H-2.2 alloantigen was shown to be controlled by two interacting genes localized within the H-2 complex. Thus, F1 hybrids prepared between parental low responder strains could yield high level immune responses. In addition, strains bearing recombinant H-2 haplotypes were used to map the two distinct genes controlling the immune response. The alleles at each locus were shown to be highly polymorphic as evidenced by the asymmetric complementation patterns observed. The restricted interactions of specific alleles was termed coupled complementation. The significance of the results in the terms of mechanisms of Ir gene control are discussed.
Group a streptococcal antigens cross-reactive with myocardium. Purification of heart-reactive antibody and isolation and characterization of the streptococcal antigen
Authors: Van De Rijn I , Sabriskie JB , McCarty M
Published: June 2004

Heart-reactive antibody (HRA) appears in the sera of experimental animals inoculated with group A streptococci as well as patients with acute rheumatic fever. Adsorption of either serum with group A streptococcal membranes will remove the HRA. Blocking experiments between these two types of HRAs have demonstrated that the antibodies are directed towards different antigenic determinants on either the same or different molecules.

To isolate and purify the antigen from the group A streptococcus cross-reactive with sarcolemmal sheaths of cardiac myofibers, it became necessary to purify the HRA from rheumatic fever patients' sera. Isolated gamma globulin containing all of the HRA was adsorbed onto human sarcolemmal sheaths. The specific HRA was released by using potassium iodide. Over 99 percent of the purified HRA was shown to bind the sarcolemmal sheath whereas less than 1 percent of the antibody would bind nonspecifically to other material.

Preparations of group A streptococcal membrane will bind HRA purified from the sera of acute rheumatic patients at levels of 97 percent or greater. The cross-reactive antigen solubilized by nonionic detergent was purified 120-fold by column chromatography. On sodium dodecyl sulfate polyacrylamide electrophoresis, the antigen was demonstrated to be composed of four polypeptides with mol wt of 32,000, 28,000, 26,000, and 22,000 daltons, respectively. Only proteolytic enzymes could destroy the antigenic determinant whereas glycosidases and lipases had no effect. The purified antigen blocked the binding of purified HRA to normal human heart sections.
Cytotoxic T cells distinguish between trinitrophenyl- and dinitrophenyl-modified syngeneic cells.
Authors: Forman J
Published: June 2004

Spleen cells sensitized against trinitrophenyl (TNP)-modified stimulator cells displayed a cytotoxic effect against syngeneic TNP-modified but not dinitrophenyl (DNP)-modified target cells. The same finding was observed in the opposite direction; that is, effector cells sensitized against DNP-modified stimulator cells did not cross kill TNP-modified targets. The specificity of the anti-TNP effector cells was confirmed in a cold target competition assay. Presensitization in vivo with hapten-modified cells followed by rechallenge and testing in vitro did not alter the specificity of the response between the haptens. These data indicate that the receptor(s) on the cytotoxic T cell can distinguish between two closely related haptenic molecules.
Induction of virus-specific modifications recognized by cytotoxic T cells is not altered by prior substitution of target cells with trinitrophenol.
Authors: Biddison W E , Snodgrass H R , Bennink J , Effros R B , Doherty P C
Published: June 2004

Cytotoxic thymus-derived lymphocytes generated after interaction with trinitrophenyl (TNP)-substituted or virus-infected cells only lyse H-2 compatible target cells modified with the component used to immunize (TNP or virus). Prior saturation of TNP-reactive sites inhibits neither the infectivity of influenza A viruses, nor the capacity of infected cells to develop antigenic changes recognized by influenza-immune T cells. The two antigens are distinct entities on the cell membrane and do not obviously compete to form interactions with H-2 molecules.
Energy metabolism and T-cell-mediated cytolysis. I. Synergism between inhibitors of respiration and glycolysis.
Authors: MacDonald H R , Koch C J
Published: June 2004

The energy requirements for T-cell-mediated cytolysis have been investigated. Cytolytic thymus-derived lymphocytes (CTL) were generated in vitro in mixed leukocyte cultures and assayed for cytotoxicity on 51Cr-labeled mastocytoma target cells. Cytolysis was only slightly reduced in the absence of exogenous glucose (less than 5 micrometer) or under conditions of extreme hypoxia (less than 0.2 micrometer oxygen). Furthermore, neither the glucose analogues 2-deoxy-D-glucose and 5-thio-D-glucose nor the respiratory antagonists sodium azide and 2,4-dinitrophenol were very effective inhibitors of cytolysis when used individually. However, these glucose analogues were highly effective in inhibiting cytolysis in the absence of oxygen, and the respiratory antagonists inhibited cytolysis to a much greater extent in the absence of glucose. In addition, synergistic effects were observed when the glycolytic and respiratory inhibitors were combined. Taken together, these results indicate that T-cell-mediated cytolysis is an energy-dependent process which can be supported by either oxidative or glycolytic energy pathways.
Influence of splenectomy on first set rejection reactions of C57BL/6 females to male skin isografts.
Authors: Streilein J W , Wiesner J
Published: June 2004

The tempo with which C57BL/6 females reject male skin isografts is determined in part by the immunogenicity of the H-Y antigen and in part by the capacity of the host to respond immunologically. Our studies indicate that the spleen plays an important role in determining the briskness of the rejection process in that splenectomy 7-30 days before grafting with male skin significantly shortens the survival time. The results of reconstitution experiments suggests that a population of cells is present in spleens of normal, but not specifically sensitized, females which can restore the conventional first set reaction in splenectomized females. It is inferred that this resident population normally operates in spleen-intact females to delay the development of specific effector responses. Lymphoid cells from H-Y antigen-sensitized, splenectomized females failed to evoke graft-vs.-host responses in males whereas similar cells from females with spleens intact did possess graft-vs.-host potential.
Antigen presentation in the murine T-lymphocyte proliferative response. I. Requirement for genetic identity at the major histocompatibility complex
Authors: Yano A , Schwartz RH , Paul WE
Published: June 2004

A method is described for stimulating proliferation in primed populations of murine T lymphocytes using antigen bound to mitomycin-C-treated spleen cells. This form of antigen presentation appears to be an active process because heat-killed spleen cells are ineffective, and because genetic similarity at the major histocompatibility complex (MHC) between the responder T cells and the presenting spleen cells is required for effective interactions. At all times examined, from day 3 to day 6 of the proliferative response, syngeneic spleen cells presented antigen better to peritoneal exudate T-lymphocyte-enriched cells (PETLES) than semisyngeneic F(1) spleen cells, which in turn could present antigen better than totally allogeneic spleen cells. Spleen cell mixing experiments demonstrated that these genetic restrictions were not the result of suppression by the ongoing mixed lymphocyte reactions (MLR) in the allogeneic and F(1) cases. Furthermore, incompatibility at the Mls locus generated a strong MLR but failed to prevent antigen presentation if the spleen cells and PETLES were compatible. Genetic mapping studies demonstrated that compatibility at only the I-A subregion of the MHC was sufficient for effective presentation of the antigen, dinitrophenylated ovalbumin. Compatibility at only the K region, or the K and D regions was not sufficient. These results support the concept that functional activation of primed, proliferating T lymphocytes requires the participation of gene products coded for by the I region of the MHC. This conclusion is consistent with a growing body of evidence which suggests that most T cells recognize antigen in association with MHC gene products.
The adoptive transfer of pregnancy-induced unresponsiveness to male skin grafts with thymus-dependent cells.
Authors: Smith R N , Powell A E
Published: June 2004

A majority of C57BL/10Sn females pregnant six or more times by syngeneic males do not reject male skin grafts. The pregnancy induced tolerance of male skin grafts was transferred adoptively to virgin recipients by thymus-dependent cells from multiparous tolerant donors.
Purification and characterization of mouse serum protein with specific binding affinity for C4 (Ss protein)
Authors: Ferreira A , Takahashi M , Nussenzweig V
Published: June 2004

A new component of the complement (C).system, with a specific binding affinity for the activated Ss-protein (C4) has been identified in mouse serum. This protein, named Ss- (or C4)-binding protein (Ss-bp), was purified about 200 times from mouse plasma.

Ss-bp is a heat stable (56 degrees C, 60 rain) β-globulin with a sedimentation coefficient in sucrose density ultracentrifugation of 10s. Its concentration in serum of adult male and female mice is 160 and 60 μg/ml, respectively.

In EDTA-plasma, Ss and Ss-bp are not associated and can be separated by chromatography in Sephadex G-200. However, in serum Ss-bp binds tightly to Ss. The bonds between these proteins cannot be reversed by chelation of divalent cations.

As a consequence of the formation of Ss/Ss-bp complexes, the properties of Ss-bp appear to be quite different in serum of mice with high (Ss-H) or low (Ss-L) levels of Ss-protein. In Ss-H serum, all of Ss- bp is bound to Ss. In Ss-L serum, Ss-bp is mostly free. Because the electrophoretic mobilities of free and complexed Ss-bp are quite different, Ss-bp appears to be polymorphic in serum (but not in EDTA- plasma). The strict dependency of the apparent electrophoretic mobility of Ss-bp on the levels of Ss in serum was demonstrated in a series of congenic mice and among the progeny of a cross between Ss-H and Ss-L strains of mice. Without exception, the slow and fast varieties of Ss-bp were associated with the Ss-L and Ss-H traits.

Ss-bp of the slow variety can be transformed into the fast variety by addition of pure human C4, or C4-sufficient guinea pig serum, to Ss-L serum. In both instances Ss-bp formed stable complexes with C4 or a C4- derived peptide. These findings highlight the binding specificity of Ss- bp for the fourth component of the complement system, and in addition they demonstrate a functional homology between the Ss-protein and C4 from two different species.
In vitro analysis of allogeneic lymphocyte interaction. I. Characterization and cellular origin of an Ia-positive helper factor- allogeneic effect factor
Authors: Delovitch TL , McDevitt HO
Published: June 2004

A soluble allogeneic effect factor (AEF) was produced by using H-2 congenic mouse strains and a serum.free cell culture medium. An AEF derived from untreated activated responder cells and irradiated stimulator cells provided helper cell function in a primary and secondary antibody response for both T-cell-depleted responder B cells and stimulator B cells. This interaction may be determined by genes situated in the I-A and I-B regions: additional K-region control was not excluded. Ia antigens, but neither H-2 nor Ig determinants are molecular constituents of AEF. The active components of this AEF consist, in part, of Ia antigens derived from both the activated responder cell population and irradiated stimulator cell population.

An AEF derived from Ia negative responder cells and irradiated T-cell- depleted stimulator cells helps a secondary antibody response of T-cell- depleted stimulator B cells but not responder B cells. This genetically restricted AEF contains Ia antigens determined by the stimulator haplotype but not the responder haplotype. The priming antigen, DNP- keyhole limpet hemocyanin, is not a component of restricted AEF. The data suggest that restricted AEF may be a product of a stimulator B cell and/or macrophage. They support the hypothesis that the recognition by allogeneic T cells of Ia antigens on B cells activates the B cell to IgG antibody production.
Genetic control of radiation leukemia virus-induced tumorigenesis II. Influence of Srlv-1, a locus not linked to H-2.
Authors: Meruelo D , Lieberman M , Deak B , McDevitt H O
Published: June 2004

A single locus, tentatively denoted Srlv-1 (susceptibility to radiation leukemia virus [RadLV]-1), confers dominant susceptibility to RadLV-induced leukemogenesis. Srlv-1 is not linked to H-2, and appears to be distinct from Fv-1 and Fv-2. Preliminary data suggest that Srlv-1 affected virus proliferation. A striking feature of this system is that Srlv-1 overrides the protection afforded by the H2D-associated dominant resistance to RadLV-induced neoplasia.
Streptococcal M protein extracted by nonionic detergent. II. Analysis of the antibody response to the multiple antigenic determinants of the M-protein molecule.
Authors: Fischetti V A
Published: June 2004

Purified streptococcal M protein extracted by nonionic detergent was used in an RIA and a solid-phase radiocompetitive inhibition assay to determine the nature of the immune response in both human beings and hyperimmunized rabbits to this complex antiphagocytic antigen. Results indicate that a type-specific response to an M antigen with the development of opsonic antibodies is the result of antibodies directed against the majority of the antigenic determinants of the molecule. Cross-reactions between certain M types on the other hand, are represented by antibodies directed against only a small percentage of these antigenic determinants. Results also suggest that avidity may play a role in the action of opsonic antibodies. However, the data indicate that factors besides avidity (i.e. sites bound by the antibodies) also seem essential for opsonization.
Antigens expressed by human B lymphocytes and myeloid stem cells.
Authors: Cline M J , Billing R
Published: June 2004

Antisera prepared against papain-digested spleen cell membranes were known to by cytotoxic for normal and neoplastic human B lymphocytes and for a majority of acute and chronic myeloid leukemic cells. It is now shown that these antisera are also cytotoxic for normal myeloid stem cells (CFU-C), thus providing a probable explanation for their occurrence in myeloid neoplasia.
Exclusive involvement of H-2D(b) or H-2K(d) product in the interaction between T-killer lymphocytes and syngeneic H-2(b) or H-2(d) viral lymphomas
Authors: Gomard E , Duprez V , Reme T , Colombani MJ , Levy JP
Published: June 2004

It was demonstrated previously that the cytolysis of murine viral lymphoma cells by anti-murine sarcoma virus (MSV) syngeneic T-killer lymphocytes was restricted by some products of the H-2 complex. The respective role of the products of different regions of the H-2 complex were studied with six H-2(b) and three H-2(d) lymphomas induced by five different type C viruses. They were tested in a classical chromium release test against anti-MSV T-killer cells obtained from different inbred strains of mice, including several H-2 recombinants. Tumors o£ the H-2(b) haplotype were lysed only when effectors and target cells have in common the D(b) region. On the contrary an identity limited to the K end of the H-2 complex is necessary and sufficient in the H-2(d) haplotype. An in vitro restimulation of the spleen cells with concanavalin A strongly increased the activity of in vivo-primed T lymphocytes but did not provide any response for in vivo-primed but nonresponder cells. Preincubation of the tumor cells with anti-H-2 sera abolished the lysis by syngeneic anti-MSV effector lymphocytes. The same results were obtained by preincubating the H-2(b) targets with anti-H-2D(b), or the H-2(d) target with anti-H-2K(d). Preincubation with anti-H-2K(b) or anti- H-2D(d) were ineffective. These results show that the T-killer/target cells interaction in the MSV system involved some products of the H-2 complex which might be different with the various H-2 haplotypes and could possibly vary according to the antigenic specificity. A specific association of a viral product with a normal cellular structure, directed by the H-2 region during the viral budding could explain the observed results.
Synthesis and distribution of H-2 antigens in preimplantation mouse embryos.
Authors: Webb C G , Gall W E , Edelman G M
Published: June 2004

Synthesis of H-2 antigens by preimplantation mouse embryos is first detectable at the late blastocyst stage. These antigens were detected using immune precipitation assays of extracts of embryos labeled by incorporation of radioactive amino acids but not by surface iodination. Experiments using isolated inner cell massess and trophoblast vesicles indicate that it is the cells of the inner cell mass that synthesize these antigens. H-2 antigens were not detected in either early blastocysts or at earlier cleavage stages.
Immune response in humans after vaccination with vaccinia virus: generation of a virus-specific cytotoxic activity by human peripheral lymphocytes
Authors: Perrin LH , Zinkernagel RM , Oldstone MBA
Published: June 2004

After vaccinia virus vaccination of human volunteers, local indurations developed within 10 days, and regional adenopathy was detected in half of the individuals. Their peripheral blood lymphocytes (PBL) harvested at different days after vaccination showed specific activity against target cells infected with vaccinia virus with a peak activity at day 7. The specificity of the cytotoxic activity was not related to HLA markers, since autologous, homologous, and heterologous infected target cells were lysed with the same efficiency. The cytotoxic activity was caused by PBL that did not rosette with sheep erythrocytes and could be depleted by more than 90 percent by removing Fc receptor-bearing cells. T-cell- depleted PBL showed a one-half to two times greater cytotoxicity than intact PBL. The cytotoxic activity could also be abrogated by more than 95 percent by rabbit Fab(2) anti-human IgG. On the other hand, nonimmune PBL lysed vaccinia-infected target cells in the presence of specific antibodies against vaccinia virus, thus demonstrating that ADCC could be efficient in lysing vaccinia-infected target cells. We conclude that after vaccination, antibody-forming cells arise and provide specific anti-viral antibody and that the cytotoxic cells detected in this reaction are K cells. These experiments suggest that antibody-dependent cell cytotoxicity may be of major importance in the recovery of man to virus infections.
Type I Escherichia coli pili: characterization of binding to monkey kidney cells.
Authors: Salit I E , Gotschlich E C
Published: June 2004

We have demonstrated binding of purified pili from a strain of Escherichia coli to Vero cell monolayers as a model of prokaryotic-eukaryotic cell adherence. Pili bound to the tissue culture in a rapid reaction that did not require enzymatic activation. Attachment occurred optimally at pH 4-5 and could be inhibited by analogues of D-mannose, anti-pili antibodies, or by preincubation of tissue cells with mannose-specific plant lectins. Binding remained after treatment of the monolayer with glycosidases, trypsin, or a protease mixture but was enhanced after neuraminidase treatment. These results indicate that bacterial binding can occur via pili which act like lectins and presumably bind to mannose-containing glycoproteins on mammalian cell surfaces.
Antibody response to the streptococcal group A-variant polysaccharide in BASILEA rabbits lacking kappa-polypeptide chains.
Authors: Weiss S , Kelus A S , Braun D G
Published: June 2004

Rabbits from a variant strain called BASILEA, in which homozygotes express only lambda-type chains and heterozygotes have normal kappa/lambda ratios, were hyperimmunized with a streptococcal group A variant vaccine. Homozygotes (bas/bas) produced antibodies with lambda-chains, heterozygotes, however, produced predominantly antibodies with kappa-chains. The incidence of restricted high responders in the BASILEA strain was high; it was probably introduced by the original mutant rather than by the loss of kappa-chains (founder effect). The degree of heterogeneity of homozygotes is similar to the heterogeneity of heterozygotes, and to that of rabbits expressing kappa-chains. This suggests that in the rabbit, the repertoire of lambda-chain genes is of similar size to that of kappa-chain genes.
Regulatory mechanisms in cell-mediated immune responses. VI. Interaction of H-2 and non-H-2 genes in elaboration of mixed leukocyte reaction suppressor factor
Authors: Rich SS , Orson FM , Rich RR
Published: June 2004

Previous studies have shown that alloantigen-activated spleen T cells produce a soluble factor which suppresses mixed lymphocyte reaction proliferative responses, and that the interaction between suppressor and responder cells is controlled by genes of the H-2 complex. However a defect in the expression of suppressor activity was identified in the mouse strain C57BL/6J. Factor prepared from alloactivated B6 spleen cells failed to suppress MLR responses of syngeneic or H-2 compatible responder cells. Unimpaired suppressor factor production by other H-2 (b) strains and failure of suppressor factor production by a B6 congenic strain, B6.C-H-2(d) isolated the defective gene to the non-H-2 portion of the genome. In addition, the defect appeared to be related specifically to inability to produce an active factor, while the capacity to respond to suppressor molecules was unimpaired. The genetic character of the non-H-2 gene action was identified in F1 hybrid studies. Initially F(1) hybrids of the nondefective histoincompatible strains were studied. Suppressor factor from F1 cells suppressed the responses of both parental strains, and parental factors each suppressed the response of F(1) cells. Adsorption of F(1) factor with Con A-activated thymocytes of either parental strain removed suppressor activity specific for that strain, leaving activity against the other parental strain intact. The data support cedominant expression and production of distinct, parental H-2 haplotype-specific suppressor molecules by F(1) suppressor cells. An F(1) hybrid of the defective B6 strain with nondefective BALB/c produced suppressor factor which was also capable of suppressing both parental strains. Production of a suppressive B6-reactive factor by F(1) cells was verified by adsorption studies. Thus it appears that non-H-2 genes of the BALB/c parent acted in a genetically dominant fashion to provide the function required for expression of B6 suppressor molecules. We conclude that multiple genes control the expression of alloactivated suppressor cell activity, with at least one gene mapped to the I-C subregion of the murine major histocompatibility complex and one or more genes mapped to the non-H-2 gene complement.
Idiotypes of inulin-binding myeloma proteins localized to variable region light and heavy chains: genetic significance.
Authors: Lieberman R , Vrana M , Humphrey W , Chien C C , Potter M
Published: June 2004

Idiotypes of inulin-binding myeloma proteins (InuBMP) were determined primarly by variable region light chains (VL) or by variable region heavy chains (VH) but needed both chains to be expressed. Recombinant molecules were used to show that individual idiotypes (IdI) of U61, E109, T957, and A4 InuBMP and cross-specific idiotypes (IdXB) of U61 were primarily determined by VL while cross-specific idiotype (IdXA) of A4 was determined mainly by VH. The assignment of genes controlling idiotypes to VH based on allotype linkage (e.g., IdXB) is dubious until the role of the L chain in determining that idiotype is assessed. IdXB has been shown to be a VL-VH marker which presumably is controlled by two unlinked genes. However IdXB can be used as a L chain marker in combinations of strains differing in their L chain genes but having the same permissive H chain genes. Conversely IdXB can be used as a H chain marker in strains having the same permissive L chain genes but differing in their H chain genes.
Enrichment of specific suppressor T cells and characterization of their surface markers.
Authors: Taniguchi M , Miller J F
Published: June 2004

A simple method is described which allows antigen-specific suppressor T cells to be enriched by greater than 100-fold. The enriched cells have the following characteristic markers: Ig-, Thy-1+, Ly-1-, Ly-2,3+, and I-J+. More than 30% of this population could be killed directly by an antiserum specific for the I-J subregion gene product in the presence of complement.
Role of IgD in the immune response and tolerance. I. Anti-delta pretreatment facilitates tolerance induction in adult B cells in vitro.
Authors: Scott D W , Layton J E , Nossal G J
Published: June 2004

Adult spleen cells from C57BL.Ige mice, which generally are resistant to in vitro tolerance induction in the B-cell compartment, became hyporesponsive (tolerant) when cultured with antigen in the presence of an anti-allotype serum. Both antigen and anti-delta had to be present for this effect, which was hapten-specific and did not occur in C57BL/L mice, which lack the Ig5-1 allotype of the delta-chain detected in this system. Preculture with anti-mu serum plus antigen, in contrast, did not cause tolerance induction in adult spleen B cells of either strain. These results suggest that the surface IgD may act as a failsafe receptor to prevent tolerance induction in adult B cells. Tolerance studies with spleen cells from mice with markedly reduced numbers of IgD+ve cells, because of regimen of repeated injections of anti-delta serum beginning at birth (delta-suppressed mice), confirmed the importance of membrane IgD in preventing tolerance, because such delta-suppressed mice were hypersusceptible to tolerance by antigen alone. Inasmuch as immature B cells lack IgD on their surface, these studies suggest that acquisition of IgD is an important maturational step in the ability of murine B cells to discriminate tolerogenic and immunogenic signals.
The interaction of Herpes Simplex Virus with murine lymphocytes. I. Mitogenic properties of herpes simplex virus.
Authors: Mochizuki D , Hedrick S , Watson J , Kingsbury D T
Published: June 2004

Herpes simplex virus (HSV) stimulates DNA synthesis in mouse spleen cultures prepared from normal, macrophage-depleted, and T-cell-depleted spleen cells, but not from thymocytes. In addition, a polyclonal antibody response is observed in HSV-infected spleen cultures. These findings indicate that the cells stimulated to undergo DNA synthesis after HSV infection appear to be the bone marrow-derived lymphocytes. The newly synthesized DNA is host cell and not of viral origin. Heat treatment and ultraviolet irradiation of HSV before addition to spleen cultures prevents the induction of DNA synthesis. We consider the use of this system as assay for the study of cell transformation by HSV and also for the study of host cell control of the expression of the viral genome.
Immunization of mice with syngeneic Moloney lymphoma cells induces separate antibodies against virion envelope glycoprotein and virus-induced cell surface antigens.
Authors: Fenyo E M , Yefenof E , Klein E , Klein G
Published: June 2004

Immunization of mice with heavily irradiated syngeneic Moloney lymphoma cells evokes antibodies against the major viral envelope antigen, gp71, and the Moloney virus-induced cell surface antigen (MCSA). A9HT cells, an L-cell subline, react with the antibodies against the viral envelope antigen only; this reaction can be completely inhibited by virus or purified gp71. Reactivity to Moloney lymphoma cells (YAC) was only partially inhibited (maximum 30%) or not at all. This can be attributed to the reaction of the YAC cells with antibodies directed against MCSA, a nonvirion cell surface component according to both biological and biochemical evidence. Antibody-induced capping of gp71 or p15(E) did not change the membrane distribution of MCSA or H-2, indicating that these antigens represent distinct entities on the cell surface. MCSA showed only minimal capping and thereby differed in behavior from both H-2 and virion antigens. gp71 could be capped by the mouse antiserum as revealed by subsequent staining with monospecific anti-gp71 antiserum. Under ordinary test conditions this reactivity is overshadowed by the reaction against MCSA. The lack of MCSA capping reflects a difference in anchorage of this antigen.
Regulation of reaginic antibody production in mice. I. Suppression by antigen of IgE antibody production in vitro.
Authors: Danneman P J , Michael J G
Published: June 2004

Regulation of IgE production by antigen in a primed murine splenic lymphocyte culture system was described. Maximum IgE antibody production was found to occur when cells were cultured in the absence of exogenously added antigen. A cells and T lymphocytes did not affect the production of anti-DNP IgE antibody. By using a hapten-carrier antigen system (DNP-EA) for priming mice in vivo, it was found that the production of anti-DNP IgE by spleen cells in vitro was inhibited by hapten when coupled to homologous (EA) or heterologous (BGG) carrier, and was not enhanced or inhibited by homologous carrier. Anti-DNP IgE antibody production by cultures depleted of macrophages or T lymphocytes was found to be as sensitive to the suppressive effects of hapten as was the IgE production by whole spleen cell cultures. Both IgM and IgG secondary anti-DNP PFC responses in vitro were enhanced by the presence of the homologous hapten-carrier or carrier alone. DNP-BGG had no effect on the anti-DNP IgM or IgG PFC responses of the cultures. These data suggest that endogenous production of antibody (IgM or IgG) was not responsible for the observed suppression of the IgE response in vitrol The experimental results presented indicate that the regulation of the IgE production by antigen in the primed mouse splenic lymphocyte cultures was a consequence of the direct interaction of hapten with IgE B cells.
Arthritis in rats after systemic injection of streptococcal cells or cell walls.
Authors: Cromartie W J , Craddock J G , Schwab J H , Anderle S K , Yang C H
Published: June 2004

Further investigation of the biological properties of streptococcal cells and their components has produced a model of erosive synovitis in rats. A single intraperitoneal injection of an aqueous suspension of whole cell sonicate of group A streptococci into Sprague-Dawley rats induced an acute arthritis which evolved into a prolonged inflammatory process characterized by several complete or partial remissions, joint deformity, and ankylosis. The toxic moiety is a peptidoglycan-polysaccharide fragment of the cell wall which persists in tissue. Histologic features of the arthritis include an acute exudative phase followed by an erosive synovitis that leads to destruction of cartilage and subchondral bone and fibrous ankylosis of the joints. The arthropathic properties of whole cell sonicates of several species of streptococci are compared along with studies of the ability of heat-killed, whole cells of groups A, B, and C streptococci to induce arthritis in rats. Whole cells induce arthritis after a latent period of 57-120 days when group A cells are injected and 7-10 days when group B cells are tested.
Antigen mediation of a late-acting suppressor T-cell activity.
Authors: Warren R W , Davie J M
Published: June 2004

Carrier-specific suppressor T cells can suppress antibody secretion by high avidity IgG plaque-forming cells (PFC) within 90 min in vitro. This process can be blocked by the inclusion of soluble carrier in the cell mixture or by the exposure of target cells to anti-carrier antibodies or pronase. Moreover, suppression can be augmented by PFC exposure to the soluble hapten-carrier conjugate. Finally, carrier specificity may be overcome by preincubation of the target population with a hapten-heterologous carrier before addition of heterologous carrier ATC. Thus, it is likely that high avidity suppression depends upon immunogen bound to the surfaces of antibody-secreting cells which serves as a target for suppressor cells or molecules.
Recovery of avian sarcoma virus from tumors induced by transformation-defective mutants.
Authors: Hanafusa H , Halpern C C , Buchhagen D L , Kawai S
Published: June 2004

Transformation-defective (td) mutants of the Schmidt-Ruppin strain of Rous sarcoma virus (RSV), which contains deletions in the gene responsible for transformation (src gene), are unable to transform chicken embryo fibroblasts in vitro. Injection of some of these td mutants into newborn chickens resulted in the formation of sarcomas from which sarcoma virus was unfailingly recovered. The possibility that transforming RSV was present in the td virus preparations was excluded by further purification of the td viruses. Morphology of the foci induced by the newly recovered sarcoma virus was distinct from that of foci induced by the parental Schmidt Ruppin strain of RSV. It is suggested that the new sarcoma virus was generated as a result of the genetic interaction between the genomes of td virus and chicken cells.
Inhibition of lymphocyte proliferation stimulated by lectins and allogeneic cells by normal plasma lipoproteins.
Authors: Morse J H , Witte L D , Goodman D S
Published: June 2004

Lipoproteins, isolated by sequential flotation at densities 1.006, 1.019, 1.063, and 1.21, were examined for their ability to inhibit human lymphocytes stimulated by allogeneic cells and by lectins (phytohemagglutinin-P and concanavalin A). All the classes of normal plasma lipoproteins inhibited lymphoproliferation when peripheral blood lymphocytes were cultured in autologous, heterologous, or lipoprotein-deficient plasma (d greater than 1.21). The rank order of inhibitory potency was intermediate density lipoprotein (IDL) greater than very low density lipoproteins (VLDL) greater than low density lipoproteins (LDL) greater than high density lipoproteins (HDL), regardless of the mode of stimulation. The concentrations of IDL, VLDL, and LDL required for complete inhibition of stimulated lymphoproliferation were considerably below the levels of each of these lipoproteins normally found in human plasma. In addition, the concentration of HDL required for 50-90% inhibition was in the range of HDL levels normally found in human plasma. Moreover, at relatively higher concentrations, lipoproteins suppressed the incorporation of [3H]thymidine into DNA below the levels seen with reseting, unstimulated lymphocytes. The results suggest that circulating lymphocytes may normally be highly suppressed by the combined effects of all the endogenous lipoproteins and that the lipoproteins may play important roles in vivo in modulating lymphocyte functions and responses.
B-cell tolerance. IV. Differential role of surface IgM and IgD in determining tolerance susceptibility of murine B cells
Authors: Vitetta ES , Cambier JC , Ligler FS , JR Kettman , Uhr JW
Published: June 2004

During ontogeny IgD appears later than IgM on splenocytes of neonatal mice (1) and at a time when mice develop a markedly increased immune responsiveness (2). Based on these observations, it was suggested that IgD serves as a "triggering" isotype for induction of immune responses, whereas surface IgM functions as a tolerizing receptor (3). To test this hypothesis, the susceptibility of adult splenocytes (which are predominantly μ(+)δ(+)[4-6]) and neonatal splenocytes (which bear predominantly IgM [μp(+); 1, 4-6]) to tolerance induction were compared. The results indicate that neonatal splenic B cells responsive to thymus dependent (TD) antigens are exquisitely susceptible to tolerance induction compared with those from adult mice (7-9). However, cells from both adult and neonatal mice were highly susceptible to tolerance induction when thymus independent (TI) antigen was used as immunogen (8). These results suggest that the major precursor for the TD response is a μ(+)δ(+)-cell which appears late in ontogeny and is resistant to tolerance induction and that the μp(+)-cell is the major precursor for the TI response and is highly susceptible to tolerance induction. Other differences between responders for TI and TD antigens have been described previously (10-12). To test this concept, adult splenocytes were treated with papain under conditions in which IgD, but not five other surface molecules, was removed (13). Such treated splenocytes were shown to be markedly susceptible to tolerance induction, resembling TD responders from neonatal animals. This experiment was interpreted as indicating that IgD confers resistance to tolerance induction on μ(+)δ(+)-cells. To prove this interpretation, it is necessary to show that specific removal of IgD with anti-δ also results in increased susceptibility to tolerance induction and that treatment with anti-μ does not have a similar effect.

In the present studies, we have removed surface IgM or IgD by antibody-induced capping and assessed the tolerance susceptibility of the treated cells. Our results demonstrate that removal of IgD, but no IgM, from TD responders increases their susceptibility to tolerance induction.
Lymphocyte culture: induction of colonies by conditioned medium from human lymphoid cell lines.
Authors: Galbraith R M , Goust J M , Fudenberg H H
Published: June 2004

The presence of phytohemagglutinin or pokeweed mitogen in cultures of human peripheral blood mononuclear cells in agar is known to stimulate the formation of lymphoid colonies. We now report that similar colonies can be induced in the absence of plant lectins upon addition of filtered and ultracentrifuged conditioned medium (CM) obtained from certain human lymphoblastoid cell lines. Colony formation required at least 6 X 10(5) mononuclear cells per milliliter, and optimum results were obtained at concentrations of 1 X 10(6) cells/ml in the presence of 20% CM (50-500 colonies per 10(6) cells cultured). Individual cells within colonies displayed uniform morphological characteristics of lymphoid cells, and the majority formed rosettes with sheep erythrocytes, suggesting that they were of T-cell type.
Migratory behavior of lymphocytes with specific reactivity to alloantigens. II. Selective recruitment to lymphoid cell allografts and their draining lymph nodes.
Authors: Emeson E E
Published: June 2004

A dual-antigen, dual-isotope assay has been used to monitor the migratory behavior of selectively labeled antiallogeneic lymphocytes in mice challenged subcutaneously in all four foot pads with semiallogeneic spleen cells. 3H-labeled anti-C3H and 14C-labeled anti-C57BL lymphocytes of DBA/2J origin were pooled and adoptively transferred to multiple groups of previously challenged DBA/2J recipients. In some of the studies, separate groups of recipients were challenged with either CDF or BDF spleen cells in all four paws, whereas in others CDF spleen cells were used to challenge the right paws of each mouse in the group and BDF spleen cells to challenge the left paws of each mouse in the group. At intervals varying from 24 to 96 h after challenge, a subgroup of four mice from each appropriate group was sacrificed and the relative numbers of anti-C3H and anti-C57BL lymphocytes present in the challenged paws, draining lymph nodes, and other tissues of each mouse were inferred from the mean 3H/14C ratios of the respective tissues of that subgroup. The results of these studies firmly establish that specific antiallogeneic lymphocytes are selectively recruited to the paws and draining lymph nodes of mice challenged subcutaneously in the foot pads with semiallogeneic spleen cells and are deleted from their circulating blood and nondraining lymph nodes. A mechanism for antigen-induced selective recruitment and its possible functional significance in tumor immunology are discussed.
A suppressor T cell of the mixed lymphocyte reaction in man specific for the stimulating alloantigen. Evidence that identity at HLA-D between suppressor and responder is required for suppression.
Authors: Engleman E G , McMichael A J , Batey M E , McDevitt H O
Published: June 2004

It has previously been shown that J.H., a human leukocyte antigen (HLA)-Dw2 homozygous multiparous woman, fails to respond in a mixed lymphocyte reaction (MLR) to her Dw1 homozygous husband W.H., and that her T cells suppress the responses of HLA matched responders to W.H. The present studies take advantage of the observation that J.H. suppressor cells resist a dose of gamma-irradiation which functionally eliminates her MLR responder cells. J.H. cells, depleted of alloreactive cells, suppress the responses of Dw2 heterozygous or homozygous cells to W.H., regardless of their associated HLA-A or B antigens. Only when W.H. or a few other cells are present as the irradiated stimulator is J.H. suppression of Dw2 responses detected. Thus, the J.H. suppressor T cell recognizes determinants in the irradiated stimulator cells as well as D locus products in the responder.
Regulatory substances produced by lymphocytes. VI. Cell cycle specificity of inhibitor of DNA synthesis action in L cells.
Authors: Wagshal A B , Jegasothy B V , Waksman B H
Published: June 2004

IDS inhibits DNA synthesis and mitosis of L cells only when present during the late G1 phase of the cell cycle, as shown with L cells synchronized by a variety of methods. This corresponds well with earlier findings that IDS inhibits DNA synthesis in mitogen-stimulated lymphocytes when present between 16 and 24 h after adding mitogen. In both cell types, the inhibition produced by IDS appears to be totally the result of elevation of cAMP level. Thus, inhibitors of cAMP phosphodiesterase work synergistically with IDS, and activators of cAMP phosphodiesterase overcome the inhibition by IDS. This paper shows that IDS raises cAMP levels in L cells only within a narrow interval of the cell cycle, around 6-8 h after mitosis. This cell cycle specificity, which may be related to appearance of receptors for IDS only at discrete times, may be important in limiting IDS action to suppression, as elevated cAMP levels have a variety of other effects during other phases of the cell cycle.