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Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we demonstrated that some V beta 6+, CD4+, Mls-1a-specific T cell clones had cytolytic activity when stimulated with anti-T cell receptor(TcR)/CD3 monoclonal antibodies (mAb), but not with targets expressing Mls-1a, although they produced lymphokines (interleukin 2 and interferon-gamma) in response to both types of stimuli. To examine the possibility that lack of cytolysis resulted from expression of the Mls-1a antigen on merely a fraction of splenic B blasts, we (a) used the B cell lymphoma LBB.3.4.16 and (b) measured esterase secretion which is generally concurrent with cytotoxic T lymphocyte (CTL) activity. The B cell lymphoma maximally stimulated the T cell clone for interferon-gamma production when responding and stimulating cells were incubated at a 1:1 ratio, but it was never killed by the Mls-1a-specific T cell clone unless TcR/CD3-specific mAb were added. Furthermore, a fivefold excess of the Mls-1a B cell lymphoma did not induce any secretion of esterase, which was observed only in the presence of the TcR/CD3-specific mAb. Comparison of the reactivity of two Mls-1a-specific T cell hybridomas expressing the same TcR at similar surface density, revealed both quantitative and qualitative differences between CD3-specific mAb and Mls stimulation of the hybridomas. A small quantitative difference in the sensitivity of hybridoma FJ22.5 to stimulation with V beta 6 or CD3-specific mAb resulted in a marked decrease in efficiency of stimulation by Mls-1a for interleukin 2 production and to inability to detect growth inhibition by Mls-expressing cells. A qualitative difference was observed when analyses of inositol phosphate production were performed under optimal conditions of stimulation of the highly responsive T cell hybridoma (FJ8.1): only stimulation with CD3-specific mAb, but not Mls-expressing cells, could induce detectable inositol phosphate production. Lack of cytolysis of Mls-1a class II-expressing B cells may have evolutionary significance in view of the recent mapping of Mls to mouse mammary tumor virus genes.
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PMID:Evidence for quantitative and qualitative differences in functional activation of Mls-reactive T cell clones and hybridomas by antigen or TcR/CD3 antibodies. 168 Jul 3

We have previously shown that the steady state levels of transcripts encoded by an endogenous mouse mammary tumor virus (MMTV) increase during LPS-induced differentiation of both normal B lymphocytes and an inducible B cell lymphoma, CH12. A large body of evidence suggests that MMTV expression is primarily limited to mammary tissues and that expression in cell lines from nonmammary tissues is accompanied by viral amplification and alterations in the transcriptional control regions of the viral long terminal repeat. We have, therefore, carefully characterized MMTV expression in CH12 cells and in other cells of the B lineage in order to determine if the expression of MMTV transcripts in differentiating B cells results from the "abnormal" transcriptional regulation seen in other nonmammary tissue. In this manuscript, we present evidence that MMTV transcripts are expressed in a variety of cells of the B lineage and that the levels of constitutive expression vary among the different cells. On the other hand, T cell lymphomas lacking amplified MMTV do not contain proviral transcripts, suggesting that MMTV transcription may be preferentially expressed in B lymphocytes. We demonstrate that MMTV transcripts are up-regulated during cytokine-mediated as well as LPS-mediated differentiation, and that most, if not all, expression is due to the activity of a single proviral gene, Mtv-9, in CH12 cells. Furthermore, the expression of MMTV transcripts in CH12 cells neither requires nor is accompanied by amplification of the provirus. Sequence analysis demonstrates that the U3 region of the expressed Mtv-9 long terminal repeat contains neither deletions nor insertions, and the well-characterized enhancer and promoter sites in the glucocorticoid response element which are known to be involved in transcriptional regulation of MMTV in mammary tissues have not been disrupted. These data suggest that the Mtv-9 locus behaves as a normal somatic gene which is differentially regulated during B cell development and differentiation. Unlike the events which lead to MMTV expression in other nonmammary tissues, B cells may express transcription factor(s) which are capable of inducing expression of endogenous MMTV proviral genes during the natural course of differentiation. Analysis of the mechanisms which control the expression of this gene should be useful in characterizing the molecular events which govern B cell differentiation.
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PMID:Molecular events in B lymphocyte differentiation. Inducible expression of the endogenous mouse mammary tumor proviral gene, Mtv-9. 215 65

Endogenous mouse mammary tumor virus (MMTV) proviral transcripts are up regulated during the normal course of B-lymphocyte differentiation. We report here that the regulatory mechanisms which lead to increased levels of MMTV transcripts in differentiating, lipopolysaccharide (LPS)-stimulated normal B cells and in the inducible B-cell lymphoma line CH12 are at least partially distinct from those controlling increases in immunoglobulin and J-chain gene expression. In studies designed to characterize the stimulatory pathways leading to MMTV expression in CH12 cells, we found that stimulation with either LPS or dexamethasone (Dex), a transcriptional activator of MMTV genes, induced not only MMTV expression but also differentiation to antibody secretion. Only Dex-induced and not LPS-induced MMTV expression and differentiation were inhibited by the glucocorticoid antagonist RU486, demonstrating that Dex and LPS stimulate B cells by distinct molecular pathways. Therefore, in B cells, MMTV expression can be regulated via either the conventional hormone receptor-dependent pathway or a hormone receptor-independent pathway. Furthermore, these results suggest that steroid stimulation of B cells can lead to alterations in the expression of other results suggest that steroid stimulation of B cells can lead to alterations in the expression of other steroid-responsive genes that can become involved in the process of B-cell differentiation.
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PMID:Lipopolysaccharide and dexamethasone induce mouse mammary tumor proviral gene expression and differentiation in B lymphocytes through distinct regulatory pathways. 216 35

We have identified and characterized an inducible in vitro subclone of the CH12 B-cell lymphoma, CH12-LBK, which appears to represent a transitional phase in the B-cell differentiation pathway. This phase, which we call the "presecretory" phase, falls between replicating B cells that are not secreting antibodies and B cells that secrete antibody at a high rate. Presecretory cells are characterized by abundant steady-state levels of immunoglobulin and joining (J) chain transcripts and of protein but low levels of mouse mammary tumor virus envelope transcripts and low rates of immunoglobulin secretion. Additional stimulation is required for presecretory cells to differentiate into cells that secrete antibodies at a high rate. The existence of cells with this phenotype suggests that high-level expression of immunoglobulin and J-chain protein does not necessarily commit a B cell to polymerize and secrete multimeric immunoglobulin. Rather, other gene products, expressed after immunoglobulin and J-chain transcripts have been upregulated late in B-cell differentiation, appear responsible for inducing high rates of antibody secretion.
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PMID:Characterization of a presecretory phase in B-cell differentiation. 249 36

We have identified a gene whose expression appears to be associated with a late stage in the differentiation of B lymphocytes into antibody secreting cells, as shown by using the inducible B cell lymphoma, CH12. Restriction mapping and partial sequencing of a cDNA clone isolated by subtraction analysis demonstrated that the clone, SC34, represents an envelope (env) gene transcript of a mouse mammary tumor virus (MMTV). In CH12 cells and in normal B cells, levels of MMTV RNA were increased after stimulation with LPS. The env transcript was the predominant MMTV RNA species and increased more dramatically than did levels of the genomic transcript. In differentiating CH12 cells, env transcripts increased as much as 20-fold above levels found in replicating, antibody nonsecreting CH12 cells. The major increase in expression appeared to be associated with B cell differentiation and not replication. By Southern blot analysis, only bands characteristic of endogenous proviruses were found in CH12, indicating that viral sequences were not amplified in this cell line. Restriction mapping indicated that the SC34 cDNA clone was a product of the Mtv-9 locus. Mtv-9 previously was shown to encode a complete MMTV provirus on chromosome 12, on which Ig heavy chain genes also are located. Increases in MMTV transcripts followed distinct kinetics and were quantitatively different from changes in immunoglobulin gene products. The expression of env RNA appears to more accurately reflect differentiation to antibody secretion in CH12 cells than does the expression of immunoglobulin gene transcripts.
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PMID:Molecular events during B lymphocyte differentiation. Induction of endogenous mouse mammary tumor proviral envelope transcripts after B cell stimulation. 284 1

In 1993 there was substantial progress in superantigen research. The following are the main achievements. (i) The life cycle of an exogenous mouse mammary tumor virus, MMTV (SW), has been clearly eluciated. (ii) X-ray crystallography of toxic shock syndrome toxin 1 has been completed. (iii) The involvement of a superantigen encoded by an endogenous mouse mammary tumor virus, Mtv-51, in the development of a B cell lymphoma has been shown in SJL mice. However, there are many unsolved questions. For example, (i) are there endogenous superantigens in man? (ii) is there any role for superantigens in the development of autoimmunity? (iii) what is the three dimensional structure of superantigens encoded by mouse mammary tumor viruses? In the near future superantigens will be exploited for therapeutic purposes in the area of autoimmunity and cancer.
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PMID:[Recent progress in superantigen research]. 796 97

Interleukin-5 (IL-5) and IL-6 have both been reported to act as B-cell differentiation factors by stimulating activated B cells to secrete antibody. However, it has not been possible to directly compare the effects of these two lymphokines because of the lack of a suitable B-cell line capable of responding to both. We have identified a clonal, inducible B-cell lymphoma, CH12, that has this property. Both IL-5 and IL-6 can independently stimulate increases in steady-state levels of immunoglobulin and J-chain mRNA and proteins, and they both induce the differentiation of CH12 into high-rate antibody-secreting cells. Nevertheless, there are significant differences in the activities of these two lymphokines. First, while IL-6 acts only as a differentiation factor, IL-5 also augments the proliferation of CH12 cells. Second, the differentiation stimulated by IL-5 but not by IL-6 is partially inhibited by IL-4. Inhibition of IL-5-induced differentiation was not at the level of IL-5 receptor expression, since IL-4 did not inhibit IL-5-induced proliferation. Third, IL-5 but not IL-6 stimulated increased mouse mammary tumor proviral gene expression in CH12 cells. These results demonstrate that while both IL-5 and IL-6 may act as differentiation factors for B cells, they induce differentiation by using at least partially distinct molecular pathways. Our results also establish that B cells characteristic of a single stage of development can independently respond to IL-4, IL-5, and IL-6.
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PMID:Interleukin-5 (IL-5) and IL-6 define two molecularly distinct pathways of B-cell differentiation. 832 Dec

The MHC class II I-A(s) positive B cell lymphomas reticulum cell sarcoma (RCS) that arise in > 90% of SJL mice by the age of 12 months have superantigen-like stimulating properties. In the present study, therefore, RCS cell lines were examined for abnormal expression of endogenous mouse mammary tumor virus (MMTV) proviruses. Extraordinarily high expression of a 1.8 kb mRNA hybridizing with the long terminal repeat (LTR) of MMTV was found in both primary lymphomas and in vitro RCS lines, but not in an SJL B cell lymphoma, NJ101, that does not stimulate syngeneic T cells, or in LPS activated SJL B cells. A cDNA was cloned from cRCS-2 and sequenced. A 31mer oligonucleotide probe, prepared based on the unique C-terminal sequence of this RCS-Mtv LTR, detected the 1.8 kb mRNA in all RCS lymphomas, while a similar probe for the C-terminal sequence of Mtv-8 LTR hybridized with the larger mRNA present in normal B cells and in NJ101. Preincubation with 19mer antisense S-oligonucleotides, prepared based on the sequences of the first two potential translation initiation sites common to both Mtv-8 and the RCS-Mtv LTR, significantly reduced the ability of RCS cells to stimulate syngeneic T cells. Moreover, transfection of NJ101 cells with the cloned RCS-MMTV cDNA conferred V beta 16 T cell stimulating properties on to these cells. It is concluded that expression of the product of this MMTV-LTR mRNA provides RCS with the strong T cell stimulating properties that it needs for its growth. These results thus identify a novel oncogenic property of MMTV-LTR.
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PMID:Linkage of superantigen-like stimulation of syngeneic T cells in a mouse model of follicular center B cell lymphoma to transcription of endogenous mammary tumor virus. 838 94

Mice harbor a family of endogenous retroviruses, the mouse mammary tumor viruses (MMTV), which encode superantigens. These superantigens are responsible for the deletion of T cells expressing certain Vbeta chains of the T-cell receptor in the thymus. Human T cells are able to recognize MMTV-encoded superantigens presented by human major histocompatibility complex class II-positive cells. Owing to this and to the similarity of the human and murine immune systems, it was speculated that human endogenous retroviruses might also code for superantigens. Recently, it was reported that a proviral clone (IDDMK(1,2)22) of the human endogenous retrovirus family HTDV/HERV-K encodes a superantigen. The putative superantigen gene was located within the env region of the virus. Stimulated by these findings, we amplified by PCR and cloned into eucaryotic expression vectors open reading frames (ORFs) which were identical or very similar to IDDMK(1,2)22. When we transfected these vectors into A20 cells, a murine B-cell lymphoma, we were able to demonstrate mRNA expression and protein production. However, we did not find any evidence that the ORF stimulated human or murine T cells in a Vbeta-specific fashion, the most prominent feature of superantigens.
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PMID:Functional analysis of the env open reading frame in human endogenous retrovirus IDDMK(1,2)22 encoding superantigen activity. 1086 49

Mouse mammary tumor virus (MMTV) superantigens (vSAgs) can undergo intercellular transfer in vivo and in vitro such that a vSAg can be presented to T cells by major histocompatibility complex (MHC) class II proteins on antigen-presenting cells (APCs) that do not express the superantigen. This process may allow T-cell activation to occur prior to viral infection. Consistent with these findings, vSAg produced by Chinese hamster ovary (CHO) cells was readily transferred to class II IE and IA (H-2(k) and H-2(d)) proteins on a B-cell lymphoma or mouse splenocytes. Fixed class II-expressing acceptor cells were used to demonstrate that the vSAg, but not the class II proteins, underwent intercellular transfer, indicating that vSAg binding to class II MHC could occur directly at the cell surface. Intercellular transfer also occurred efficiently to splenocytes from endogenous retrovirus-free mice, indicating that other proviral proteins were not involved. Presentation of vSAg7 produced by a class II-negative, furin protease-deficient CHO variant (FD11) was unsuccessful, indicating that proteolytic processing was a requisite event and that proteolytic activity could not be provided by an endoprotease on the acceptor APC. Furthermore, vSAg presentation was effected using cell-free supernatant from class II-negative, vSAg-positive cells, indicating that a soluble molecule, most likely produced by proteolytic processing, was sufficient to stimulate T cells. Because the membrane-proximal endoproteolytic cleavage site in the vSAg (residues 68 to 71) was not necessary for intercellular transfer, the data support the notion that the carboxy-terminal endoproteolytic cleavage product is an active vSAg moiety.
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PMID:Intercellular transfer of a soluble viral superantigen. 1095 23


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