Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0079731 (B-cell lymphoma)
 16,671 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain maternal/infant pairs, as well as other high-risk adults, develop a host-response HIV-1 infection characterized by circulating and tissue infiltrative CD8 T-cell lymphocytosis, termed Diffuse Infiltrative Lymphocytosis Syndrome (DILS). DILS primarily occurs in the salivary glands, lungs, renal interstitium, and gastrointestinal tract. DILS differs from Sjogren's syndrome in the degree of salivary gland enlargement, high frequency of extraglandular manifestations, paucity of autoantibodies, and distinct immunogenetic associations. Salivary gland B-cell lymphoma is a complication common to both conditions. The circulating CD8 T cells in DILS have a memory phenotype. Egress into target tissues involves adhesion molecule receptor-ligand interactions, apparently in response to the local presence of HIV-1. Immunogenetic predisposition involves interaction between both MHC classes I and II loci. This disease appears to reflect a specific host response that leads to persistence of monocyte-tropic, rather than T-cell-tropic, HIV-1 strains, in an analogous fashion to Visna Maedi virus disease in sheep. The development of DILS in children appears to be regulated in a dominant fashion by maternally or paternally inherited MHC class II alleles in response to transplacentally or perinatally acquired maternal HIV-1 strains.
 ...
PMID:Diffuse infiltrative lymphocytosis syndrome in children and adults infected with HIV-1: a model of rheumatic illness caused by acquired viral infection. 128 93

Methylation patterns in the major histocompatibility complex (MHC) class II Eb locus have been analyzed in cell lines representative of different cell types; in particular those with phenotypes found at various stages of B cell development. A series of variant B cell lymphoma lines which serves as a model in which to investigate mechanisms regulating class II gene expression in normal peripheral B cells has been examined. Eb methylation patterns have also been determined in various healthy mouse tissues. The pattern of methylation of the Eb locus varies between different cell lines and tissue types such that hypomethylation is associated with gene expression. There appears to be a methylation pattern which is permissive for class II gene expression and which is characteristic of a variety of cell lines, but is lost in cell lines representing terminally differentiated class II nonexpressing plasma cells. Another methylation pattern has been identified which is found in cloned cell lines selected for expression of very high levels of cell surface class II product. The patterns of methylation associated with MHC class II expression involve changes in methylation sites located within the first intron and several kilobase pairs 5' of the promoter, but no changes were observed in the 3' end of the locus. Moreover, the different methylation patterns do not map to the prominent CpG rich cluster located 5' of the Eb promoter and which remains completely methylated regardless of transcriptional status.
 ...
PMID:Hypomethylation of MHC class II Eb gene is associated with expression. 163 42

A 72/74-kDa peptide binding protein (PBP72/74) was previously described which plays a role in the processing and/or presentation of Ag, possibly by facilitating the association of processed Ag with the MHC class II molecules. PBP72/74 was recently shown to be related to the 70-kDa family of heat shock proteins (hsp70), whose members show the general characteristic of binding to denatured or inappropriately folded proteins. Here we describe the cellular and subcellular distribution of PBP72/74. By flow cytometry with PBP72/74-specific rabbit antisera, PBP72/74 is detected on the surfaces of mouse Ig+ B cells and MAC-1+ macrophages. PBP72/74 74 was not detected on the surfaces of Thy-1+ T cells or NK1.1+ NK cells. The cell surface expression of PBP72/74 does not require MHC class II expression. Indeed, the Ia- variant B cell lymphoma cell line, M12.C3, expresses PBP72/74 at levels equivalent to that of the Ia+ parent cell line, M12.4.1, from which it was derived. Furthermore, the fibroblast L cell line, DAP.3, shows no cell surface expression of PBP72/74, nor do DAP.3 lines transfected with and expressing genes encoding the alpha- and beta-chain of the I-Ad and I-Ed molecules. Moreover, treatment of B cells with either IL-4 or LPS, which increases Ia expression severalfold, does not affect PBP72/74 expression. Thus, PBP72/74 cell surface expression appears to be a property of B cells and macrophages, independent of Ia expression. In addition, the B cell surface expression of PBP72/74 is not altered by stress in the form of heat shock. Thus, PBP72/74 appears to be a constitutive noninducible member of the hsp70 family. By immunoelectron microscopy, PBP72/74 is detected in approximately 36% of early endocytic vesicles into which surface Ig is internalized after binding to anti-Ig antibodies. This compartment was previously shown to contain class II en route to the cell surface associated with invariant chain and the proteases cathepsin B and D and is suggested to be a subcellular site of antigen processing. PBP72/74 is also found associated with the plasma membrane, endoplasmic reticulum, and membranes proximal to the Golgi stacks. The cellular and subcellular distribution of PBP72/74 is consistent with its playing a role in the processing of presentation of Ag with the MHC class II molecules.
 ...
PMID:Cellular and subcellular distribution of PBP72/74, a peptide-binding protein that plays a role in antigen processing. 198 75

Cyclosporine (CsA) was examined for its ability to inhibit alloantigen presentation by spleen cells in a primary mixed lymphocyte reaction; by gamma interferon-induced P388.D1 macrophages to an alloreactive T cell clone; and by a B cell lymphoma, B1D.beta to an alloreactive T cell hybridoma. Alloantigen-presenting cells were treated with CsA or its inactive analogs for 2 hr, washed extensively (four times), and added to the T cells. Using this protocol, CsA maximally inhibited allorecognition by the T cells at 1000 ng/ml in all three systems. An HPLC assay for CsA cell failed to detect any significant CsA carryover into the T cell assays. Supernatant transfer experiments also failed to demonstrate CsA carryover in the more sensitive T cell hybridoma assay. These transfer experiments also failed to demonstrate the generation of inhibitory factors during the assay. Northern blot analysis and a cell-surface ELISA failed to observe any decreases in MHC class II induction in/on P388.D1 cells with CsA present during the induction. Due to the lack of detectable (less than 10 ng/ml) CsA carryover, we hypothesize that CsA has a direct effect on the formation of stimulatory MHC class II in our alloreactive systems.
 ...
PMID:Inhibition of alloantigen presentation by cyclosporine. 215 62

The staphylococcal exotoxin toxic shock syndrome toxin-1 (TSST-1) has potent stimulatory effects on murine and human lymphocytes. This is the consequence of TSST-1 binding to major histocompatibility complex (MHC) class II molecules and the engagement in a V beta-restricted fashion of the T cell receptor by the TSST-1-MHC class II complex. Using radioligand and functional assays we have recently shown that TSST-1 binds to all HLA-DR (n = 14), HLA-DQ (n = 2) and HLA-DP (n = 2) phenotypes tested. In this study, we have examined the ability of murine MHC class II molecules to bind TSST-1. Specific high-affinity binding of TSST-1 was detectable to unfractionated BALB-c (H-2d) and C57BL/6 (H-2b), but not to C3H (H-2k) spleen cells. The Kd of this binding estimated from Scatchard analysis was in the same nanomolar range as the Kd of binding of TSST-1 to HLA-DR. Binding of 125I-labeled TSST-1 to BALB/c-derived B cell lymphoma lines and to L cell transfectants correlated with the expression of I-A molecules, but not with the expression of I-E molecules. Furthermore, I-A+, I-E- cells but not I-A-, I-E+ cells were able to support TSST-1-induced T cell proliferation. The binding affinity of TSST-1 for I-Ak appears to be much lower than for I-Ad. L cell transfectants expressing hybrid DR alpha: I-E beta k molecules, but not those expressing I-E alpha k: DR1 beta molecules, could bind TSST-1 and efficiently support TSST-1-induced T cell proliferation. This suggests that minor differences in the highly homologous I-E alpha and DR alpha chains are critical in determining the affinity of the MHC class II molecule for TSST-1. These results demonstrate that the binding of TSST-1 to MHC class II molecules in the mouse, in contrast to humans, is strongly influenced by phenotype. Analysis of the molecular basis of these differences may help to localize staphylococcal exotoxin binding sites on MHC class II molecules.
 ...
PMID:Binding of toxic shock syndrome toxin-1 to murine major histocompatibility complex class II molecules. 220 97

Idiotypic IgM derived from a B cell lymphoma can act as a tumor-associated Ag, in that immunization with this purified protein generates an anti-idiotypic immune response that specifically suppresses tumor development. Spleens of immune mice contain T cells that proliferate in response to idiotypic IgM. However, idiotypic Ag is presented to the T cells most efficiently in its natural form at the surface of the lymphoma cells, than as soluble IgM plus presenting cells. Variant tumors that display either little or no idiotypic IgM at the cell surface, but which are otherwise indistinguishable from parental tumor, induce a weak response or fail to stimulate the T cells, respectively. Anti-idiotypic lines and clones have been derived from the splenic T cells by growth in the presence of irradiated tumor cells. Phenotypic analysis revealed that cells from both lines and clones express CD3 and CD4 Ag, but not CD8. Recognition of tumor Id, which required no added presenting cells, was inhibited by antibody against MHC class II Ag, and variably by anti-CD4. Proliferative responses were inhibited by anti-idiotypic antibodies, but also by antibodies against the constant region of the mu H chain, indicating that perturbation of the surface IgM abrogates availability of idiotypic determinants to the T cells.
 ...
PMID:Recognition of a B cell lymphoma by anti-idiotypic T cells. 224 20

Although the MHC class II genes are known to be regulated transcriptionally, the relative rates of transcription of the four classical class II genes in different cell types have not been investigated. Using nuclear transcriptional analysis, we have investigated the transcriptional rates of the class II genes in the macrophage cell line WEHI-3, normal bone marrow-derived macrophages, L-929 cells, and two different B cell lymphoma lines. Kinetic analysis of class II transcription in IFN-gamma-treated WEHI-3 cells revealed a 4-h delay, followed by a rapid increase in transcription over the next 20 h. A significant basal level of class II transcription, apparent in bone marrow derived macrophages, was also further enhanced by IFN-gamma treatment. None of the class II genes were transcribed in L cells, whereas all class II genes were transcribed constitutively in the B cell lines. In both B cell lines and macrophages, the four class II genes were found to be transcribed at different rates from one another, but the only gene showing a consistent pattern in multiple experiments was A-alpha, always showing the highest rate. We also investigated the effect of protein synthesis inhibition on class II transcription. Cycloheximide treatment of WEHI-3 cells did not inhibit IFN-gamma-induced transcription of the class II genes within 8 h, suggesting that IFN-gamma acts on pre-existing trans-acting factors, rather than inducing their synthesis. In contrast, treatment of B cells with cycloheximide for 8 h significantly reduced class II transcription, suggesting that, in B cells, continuous synthesis of a labile trans-acting factor is required for constitutive expression. These data support the notion that class II expression in B cells is mediated by trans-acting factors distinct from those found in macrophages.
 ...
PMID:MHC class II transcription in different mouse cell types. Differential requirement for protein synthesis between B cells and macrophages. 249 89

We have targeted CD4+ cytotoxic Th (Th/c) lymphocytes to a B cell lymphoma, through the use of a bispecific antibody containing binding sites for both the CD3 complex on the Th/c and the Id on the surface Ig of the B lymphoma (anti-CD3-anti-Id). Cloned, keyhole limpet hemocyanin (KLH)-specific Th/c cells were nonspecifically activated by the anti-CD3-anti-Id conjugate to lyse the Id+ B lymphoma A20-HL. This cytotoxicity was not inhibited by antibodies to CD4 or LFA-1 alpha molecules. The anti-CD3-anti-Id conjugates also induced non-lytic Th clones to become cytotoxic, a function not elicited when these cells were activated specifically by Ag. We compare this model to our previously described system where we targeted the KLH-specific Th/c cells to the Id+ B lymphoma A20-HL via a conjugate consisting of KLH covalently linked to the anti-Id antibody (KLH-anti-Id). The mechanism involved processing and presentation of KLH by the A20-HL target. This Ag-specific cytotoxicity was MHC class II restricted and was inhibited by antibodies to the CD4 molecule. In both systems, activation of the Th/c cells resulted in bystander killing of tumor but not normal targets. These results may have important implications for the use of Th/c cells in tumor immunotherapy.
 ...
PMID:The targeting of CD4+ T lymphocytes to a B cell lymphoma. A comparison of anti-CD3-anti-idiotype antibody conjugates and antigen-anti-idiotype antibody conjugates. 252 40

The stimulation of T cells by staphylococcal enterotoxins (SE) is strictly dependent on major histocompatibility complex (MHC) class II-bearing cells. The interaction between SE and MHC class II molecules was studied on the human B cell lymphoma Raji and its MHC class II-negative variant RJ 2.2.5. Affinity purification with SEA and SEB matrix allowed the isolation of HLA-DR-like molecules from detergent lysates of 125I surface-labeled Raji cells, but not from RJ 2.2.5 cells. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis also revealed preferences in the binding of other SE such as SED, SEE and toxic shock syndrome toxin 1 to DR-like molecules, SEC2 to HLA-DQ-like molecules and SEC3 to DR- and DQ-like molecules. Preadsorption of the different MHC class II MHC isotypes confirmed the preferential binding of SEA to DR and of SEC2 to DQ. The implications of these findings for the understanding of SE-induced T cell activation and the potency of SE as a tool in the study of MHC class II antigens are discussed.
 ...
PMID:Different staphylococcal enterotoxins bind preferentially to distinct major histocompatibility complex class II isotypes. 259 4

Cross-linking of membrane IgG2a or IgD on the B cell lymphoma A20.1 resulted in the elaboration of lymphokines which were able to support the growth of HT-2 cells and to induce increased Ia expression on resting B cells. Unstimulated A20.1 cell did not produce detectable levels of lymphokine activity. Lymphokine secretion did not occur in response to cross-linking of MHC class II (Ia) or class I (H2K) molecules. The kinetics for secretion were rapid, with detectable levels of lymphokine arising within 3 to 4 h of stimulation. Maximal lymphokine production was reached by 8 to 10 h. Soluble intact anti-Ig antibodies failed to stimulate lymphokine production due to Fc-mediated effects. This was concluded based on the fact that soluble F(ab')2 fragments of anti-IgG, but not soluble intact antibody, stimulated the production of lymphokine by A20.1 cells. Based on serologic criteria, membrane Ig cross-linking by ligand induced secretion of IL-2 but not IL-4 by A20.1 cells. Induction of Ia expression by resting B cells in response to A20.1 supernatant was not mimicked by stimulation with IL-1, -3, -5, or -6 either singly or in combination. Furthermore, preliminary physicochemical characterization revealed that the Ia-inducing factor in A20.1 supernatant has a molecular weight greater than 50,000. These data suggest that the Ia-inducing activity is a novel lymphokine. Thus, this report describes the first evidence for the existence of a B cell tropic lymphokine produced by B cells in response to Ag receptor-mediated signal transduction.
 ...
PMID:Production of multiple lymphokines by the A20.1 B cell lymphoma after cross-linking of membrane Ig by immobilized anti-Ig. 266 89


1 2 3 4 5 6 Next >>