Generation of heavy chain-loss mutants in a B cell hybrid mediated by syngeneic idiotype-specific spleen cells.
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Abstract Idiotype-specific spleen cells from appropriately primed BALB/c mice cause a marked and irreversible suppression of the membrane and secreted forms of idiotype-positive immunoglobulin (Ig) of an antigen-specific B cell hybrid clone (2C3E1). The suppression of this BALB/c B cell line has been observed in vitro and in vivo, and appears to require intimate contact between effector spleen cells and target 2C3E1 cells. The observed suppression in the 2C3E1 cell line is due to an induced mutation or a selection of pre-existing mutants within the 2C3E1 cell population, because the resultant light and heavy chain-loss variants are phenotypically stable in vitro and in vivo in the absence of any further active suppression. Biochemical analysis of the 2C3E1 cells after this suppression indicates that all of the variants are negative for the production of idiotype-positive Ig. Heavy chain synthesis by the variants is almost totally eliminated, and light chain synthesis is decreased by 10 to 90%. Spleen cells from identically primed nude mice do not induce any alteration in the 2C3E1 cell line, suggesting that induction or selection of the heavy and light chain-loss mutants requires the presence of mature T lymphocytes. The generation of idiotype-negative 2C3E1 variants during the period of tumor growth in the spleen (but not elsewhere) may represent one mechanism by which this tumor escapes the host's immune recognition.Keywords:
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We have isolated a novel enhanced-nodulating mutant astray (Ljsym77) from Lotus japonicus. The name astray derives from the non-symbiotic phenotype of this mutant, agravitropic lateral roots that go “astray” against gravity. In this report we evaluated the symbiotic aspects of this mutant in detail. The astray mutant developed approximately twice the number of nodules on a wider area of roots compared with the wild type. Furthermore, the astray mutant demonstrated early initiation of nodule development, which is an unprecedented symbiotic phenotype. The astray seedlings showed normal sensitivity to the general inhibitors of nodulation such as ethylene and nitrate. These results indicate that the astray mutant is distinct from the hypernodulating mutants reported previously, and that the ASTRAY gene acts as an early and negative regulator in the cascade of nodule development.
Lotus japonicus
Nodule (geology)
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The induction of tolerance in an anti-idiotypic response was attempted by in vivo exposure to excess idiotype. Monoclonal immunoglobulin from the anti-p-azobenzenearsonate (ABA) hybridoma R16.7 was used as a representative of cross-reactive idiotype-positive (CRI+) antibodies because this hybridoma protein (HP) shares one or more closely related public idiotypic determinants with the serum CRI in A/J mice. Immunologic unresponsiveness was established by a single injection of the R16.7 idiotype and persisted for at least 6 wk. The level of circulating anti-idiotypic antibodies in tolerized A/J mice was significantly depressed after immunogenic challenge with eigher antigen, ABA-keyhole limpet hemocyanin (KLH), or the idiotype R16.7 HP. Experimental depletion of anti-idiotypic antibodies by tolerization allowed assessment of immunoregulation within this altered idiotype-anti-idiotype network. Deregulation of idiotype expression in tolerized mice challenged with ABA-KLH was manifest with up to 96% of the anti-ABA antibodies cross-reacting with the R16.7 idiotype. This selective enhancement of a major idiotype was accomplished without substantial alteration of the level of the overall anti-hapten response. Both the unresponsiveness established in anti-idiotypic antibody-producing cells and the enhanced synthesis in idiotype-producing cells were stable upon adoptive transfer into lethally irradiated, syngeneic recipients. Finally, previous immunization with the antigen ABA-KLH interfered with the induction of unresponsiveness to the idiotype. This interference is presumed to be mediated by prior activation of anti-idiotypic cells and/or antibody because injection of antigen with tolerogenic idiotype did not abrogate tolerance induction.
Immunoglobulin Idiotypes
Hapten
Keyhole limpet hemocyanin
Idiotopes
Adoptive Cell Transfer
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Abstract A requirement for idiotype matching was reported such that carrier‐primed T helper cells from mice, which are unable to produce an idiotype (idiotype‐negative) because of genetic reasons or adult anti‐idiotype or neonatal anti‐μ antibody treatment, did not provide helper function for an idiotype‐positive antibody response. We have analyzed the requirement for idiotype matching in the response to phosphorylcholine by using mice which are idiotype‐negative because they were injected with anti‐idiotype antibody shortly after birth. Carrier‐primed T cells from such animals supported idiotype‐positive responses when mixed with normal or primed B cell populations and challenged with appropriate antigen; these responses were quantitatively and qualitatively similar to those obtained with T cells from idiotype‐positive animals. These results demonstrate no requirement for idiotype matching and suggest that the procedure used to establish an idiotype‐negative T cell donor may be decisive in showing a requirement for idiotype matching.
Immunoglobulin Idiotypes
Phosphorylcholine
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We have investigated the responses of two closely related human colon tumour lines (clone A and clone D) to hyperthermic cell killing in vitro under two conditions of environmental acidity (pH values 7.40 and 6.75). At pH 7.40, under prolonged exposure to 42.5 degrees C, both lines exhibited biphasic response curves with thermotolerance appearing at about 4 h of continuous heating. It was found that the clone D human tumour line was more resistant to hyperthermic inactivation than the clone A line. At pH 6.75, both lines exhibited increased sensitivity to heating killing at 42.5 degrees C, but it was found that the effect was unequally demonstrated by the two human tumour lines (i.e. decreased pH was not acting simply as a dose modifying agent). Specifically, clone A exhibited a much greater hyperthermic sensitivity in the thermotolerant region of survival (i.e. a heating time of 4 h or more) than did clone D. Clinically, this result would suggest that although potential pH sensitization of heterogeneous tumours to hyperthermic cell killing may vary in a random manner among tumour cell subpopulations within a given tumour, the increased heat sensitivity found may produce isosurvival results for equal heating times for the different subpopulations.
clone (Java method)
Colon carcinoma
Human cell
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Abstract A procedure is described for producing ascites containing both high concentrations of antibodies and immunologically active leukocytes. In mice that were immunologically suppressed with respect to a cross‐reactive idiotype, the ascitic cells were found to be very active in adoptively transferring the suppressed state to mildly irradiated, syngeneic recipients and simultaneously transferring the capacity to produce the “private” idiotype characteristic of the donor's anti‐ p‐azophenylarsonate antibodies. The participation of both T and B cells is therefore suggested. As few as 2 × 10 6 cells were sufficient for suppression and for inducing the production of the private idiotype in the recipient, in concentrations comparable to that of the donor mouse. A single donor can thus be used to colonize many recipients with the private idiotype, without sacrifice of the donor. The method should be useful in structural studies of antibodies of a given specificity with different idiotypes, and for investigations of the mechanism of idiotype suppression, as well as other studies in cellular immunology.
Adoptive Cell Transfer
Ascitic fluid
Immunoglobulin Idiotypes
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Immunoglobulin Idiotypes
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The afforestation experiment of 21 poplar clones was conducted in Yiling District of Yichang City located in the western mountain areas of Hubei.The results showed that the five clones including clone 'Lushan',clone 'M81-18',clone '351',clone '375' and clone 'Zhonghan-17' were of excellent characteristics in growth and stable in the areas and not only suitable for intensive short-rotation plantation but also suitable for Short-rotation plantation.However,7 clones of 21 clones including clone 'Zhongjia-8',clone 'Zhongjia-5',clone 'Zhongjian-1',clone 'Zhongjian-3',clone 'Tianyan',clone 'Liaohe' and clone '108' were unsuitable for their lower survival rate and slow growth.The results provided a good basis for the selection of superior poplar clones in the western mountain areas of the Hubei.
clone (Java method)
Afforestation
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Abstract The anti‐PC antibodies of BALB/c origin bear predominantly the idiotype characteristic of the phosphorylcholine (PC)‐binding T15 myeloma protein. Sera from one‐day‐old BALB/c mice contain lower amounts of T15 idiotype than sera from adult mice, and, unlike the latter, they also contain detectable amounts of anti‐T15 antibodies. By 2 weeks of age the anti‐T15 antibodies are no longer detectable while the T15 idiotype has reached adult levels. Injection of neonatal mice with anti‐idiotypic antibodies renders them unresponsive to PC until the 15th week of life. Furthermore, this treatment induces a chronic suppression of the T15 idiotype, since on recovery from unresponsiveness, the neonatally suppressed mice produce anti‐PC antibodies which are predominantly T15‐negative. In contrast, treatment of adult mice with anti‐idiotypic antibodies induces only a transient state of unresponsiveness to PC, and the antibodies produced upon recovery bear the T15 idiotype. These findings are discussed in the context of idiotype anti‐idiotype interactions and their possible role in immunoregulation.
Phosphorylcholine
Immunoglobulin Idiotypes
clone (Java method)
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