Gene/Protein Disease Symptom Drug Enzyme Compound
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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.
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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

The purpose of this research was to determine whether prostaglandin E2 (PGE2), a major product of macrophages which can kill certain murine B cell lymphomas, induces death by a necrotic mechanism or by an alternate pathway called apoptosis. CH31 is a phenotypically "immature" B cell lymphoma which resembles immature neonatal B cells in its susceptibility to killing by reagents which cross-link surface immunoglobulin (sIg). In the present study we first show that PGE2, but not the closely related prostanoid, PGF2 alpha, kills CH31 lymphoma cells. In contrast, CH12, a phenotypically "mature" lymphoma which is not negatively affected by sIg cross-linking, is not induced to die after exposure to PGE2. Agarose gel electrophoresis demonstrated that the DNA of PGE2-treated CH31, but not CH12 cells, is cleaved into characteristic 200 base pair oligonucleosomal fragments indicative of an apoptotic mechanism of death. However, a necrotic form of death, indicated by random DNA cleavage which produces a smear following electrophoresis, could be induced by treatment of CH12 or CH31 with anti-class II MHC antibodies and complement. The apoptotic mechanism of CH31 cell killing by PGE2 was confirmed using scanning electron microscopy which demonstrated the unique membrane blebbing and bubbling pathognomonic of this form of death. Finally, using a recently devised flow cytometric method to study apoptosis in heterogeneous cell populations, we compared the ability of anti-IgM, PGE2, or PGF2 alpha to induce apoptosis in B lymphocytes from neonatal or adult mice. Anti-IgM, and to a lesser extent PGE2, but not PGF2 alpha, induces apoptosis in a fraction of neonatal B cells. None of these treatments induced cell death in B lymphocytes from mature mice. Overall, these observations suggest that PGE-secreting cells such as macrophages, which inhabit the B cell microenvironments of lymphoid organs, may eliminate a subset of immature B lymphocytes and may be important in controlling the spread of PGE-sensitive malignant B lymphoma cells.
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PMID:Prostaglandin E2 induces apoptosis in immature normal and malignant B lymphocytes. 162 42

We examined stimuli which are required for the induction of in vitro proliferation of follicular lymphoma cells, a low grade non-Hodgkin's B cell lymphoma characterized by a specific chromosomal translocation, t(14;18)(q32;q21), and by in vivo growth of the lymphoma cells in germinal center-like follicles infiltrated with CD4+ T cells. The purified follicular lymphoma cells, which are morphologically uniform, small, and dense, did not respond to stimulation with soluble lymphokines in the absence of T cells. Vigorous in vitro proliferation of follicular lymphoma cells was induced, however, when the follicular lymphoma cells were cultured with a CD4+ T cell clone which recognized alloantigens expressed by the lymphoma cells. This response required B-T cell contact, and was inhibited by anti-class II but not by anti-class I MHC mAb, indicating that these neoplastic B cells behaved as normal B cells and responded to normal activation and differentiation signals from T cells. After the cognate B lymphoma-T cell interaction occurred in culture, addition of IL-2 or IL-4 enhanced the proliferation of the tumor cells. These results, with a monoclonal and homogeneous population of B cells, affirm the idea that cognate interaction between B cells and Th cells is required for the effective activation of resting B cells. Moreover, these results suggest that a critical host-tumor interaction occurs in vivo, and that the polyclonal CD4+ T cells that infiltrate follicular lymphomas play a role in sustaining rather than inhibiting tumor growth in vivo. If so, therapies directed not only against the neoplastic cell but also against specific T cells and their cognate interactions with tumor cells may have a rationale.
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PMID:Induction of proliferation of human follicular (B type) lymphoma cells by cognate interaction with CD4+ T cell clones. 196 51

Antigen processing is an essential step in the presentation of most protein antigens to class 2 MHC restricted T cells, but many of the details of processing remain unknown. In this study we show that a whole cell lysate, as well as membrane fractions from an antigen-presenting B cell lymphoma, can process ovalbumin. In this system native ovalbumin incubated with these membranes at acidic pH can be presented to an antigen-specific hybridoma by gluteraldehyde-fixed, antigen-presenting cells. This processing is inhibited by pepstatin, a selective inhibitor of aspartyl proteases. This is the first study of processing by subcellular fractions, and this cell-free system will provide a good model in which to dissect further the molecular requirements of antigen processing.
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PMID:A cell-free model system for the study of antigen processing. 248 48

We have targeted protein antigens to antigen-presenting cells in vitro by using antibody heteroaggregates containing an antibody against a protein antigen covalently crosslinked to an antibody against a target structure on the surface of the antigen-presenting cells. Antigen presentation was assessed by measurement of lymphokine released by antigen-specific T cell hybridomas. Depending on the experimental conditions, the crosslinked antibodies decreased the amount of antigen required to give a response by the hybridomas by factors of 10(2) to 10(3). Enhanced presentation occurred when antigen was targeted to MHC class I and class II molecules, surface immunoglobulin, or Fc gamma receptors on the surface of the murine B cell lymphoma-hybridoma, TA3. An enhancement of antigen presentation also occurred when antigen was targeted to surface IgD, or class I and class II MHC molecules on murine splenic B cells, and when antigen was targeted to class I and class II molecules on irradiated adherent spleen cells. No response was seen when antigen was targeted to Fc gamma R on B cells or adherent spleen cells. The ability of each crosslinked antibody to enhance presentation paralleled the total amount of each that bound to the surface of the antigen-presenting cells. Antigen presentation, mediated by crosslinked antibody, was antigen-specific and I-A restricted. The presentation of one antigen by using crosslinked antibody did not result in enhanced presentation of a second, bystander antigen. These results suggest that a novel means of stimulating immune responses may be possible in vivo, by targeting antigen to surface structures on antigen-presenting cells.
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PMID:Targeted antigen presentation using crosslinked antibody heteroaggregates. 295 30

Careful analysis of affinity-purified class II molecules (Ia Ag) from the murine MHC revealed the existence of a set of associated molecules that consistently co-purified with the Ia Ag. SDS-PAGE revealed that molecules of Mr of 41 to 43 kDa and 56 to 58 kDa were associated with the affinity-purified I-Ak Ag from the AKR B cell lymphoma AKTB-1b. Two-dimensional electrophoresis (IEF vs SDS-PAGE) allowed further characterization of four molecules in the 41- to 43-kDa range and two in the 56- to 58-kDa range. All co-purifying proteins had isoelectric points between 5.2 and 6.2. The specificity of the association of the co-purifying molecules with the I-Ak Ag was established by using two criteria. First, with the exception of actin, proteins co-purifying with the I-Ak molecule were not found in samples of affinity-purified class I (H-2Kk) Ag or membrane Ig from the AKTB-1b lymphoma. Second, the use of the amino group-reactive homobifunctional cross-linker 3,3'-dithiobisproprionimidate with crude membranes from AKTB-1b increased the relative amount of materials co-purifying with I-Ak. The use of the membrane-impermeant cross-linker 3,3'-dithiobis(sulfosuccinimidyl) proprionate provided evidence that the interaction between I-Ak and one or more of the co-purifying components occurs on the cytoplasmic face of the membrane. Two of the co-purifying molecules have been identified. The major material in the 41- to 43-kDa range was partially sequenced, leading to its identification as cytoplasmic actin. One of the components in the 56- to 58-kDa range was tentatively identified as one of the isozymes (RII) of the regulatory subunit of the cAMP-dependent protein kinase, based on the use of the photoaffinity label 8-azido-cAMP.
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PMID:Biochemical characterization of proteins that co-purify with class II antigens of the murine MHC. 316 51

To study the role of class II MHC expression in mouse lymphomagenesis, we examined the cell surface expression of I-A/E antigens on 24 spontaneous or murine leukemia virus (MuLV)-induced mouse B10.A (I-Ak, I-Ek) B cell lymphomas. Two primary B10.A B cell lymphomas were observed with strong I-Ek expression but with only minimal cell surface I-Ak expression. Both tumors are readily transplantable in syngeneic mice, with maintenance of their I-A-, I-E+ phenotype. Strikingly, one I-A-, I-E+ B cell lymphoma contains a (11; 17) translocation with a breakpoint on chromosome 17 that is localized within or very close to the H-2 complex. DNA of both tumors contains normal restriction enzyme fragments of the A alpha and A beta genes. Northern blot analyses indicated that one I-A-, I-E+ tumor strongly expressed A alpha, E alpha, and E beta mRNAs but possessed only a weak expression of A beta mRNA. The other B cell lymphoma showed A beta, E alpha, and E beta mRNA expression but only minimal A alpha mRNA expression. In 11 primary B10.A B cell lymphomas with a normal I-A+, I-E+ phenotype, no imbalances in A alpha/A beta mRNA levels were observed. The implications of these findings for the role of class II MHC expression in mouse B cell lymphoma-genesis are discussed.
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PMID:Imbalanced MHC class II molecule expression at surface of murine B cell lymphomas. 348 45

Bispecific monoclonal antibodies (bsAbs) that recognize CD3 with one arm and a tumor associated antigen with the other arm can retarget T-cells toward tumor cells in an MHC independent manner, thereby combining the specificity of monoclonal antibodies with the power of the cellular immune system. B-cell malignancies are particularly attractive as targets for anti-CD3-based bsAb therapy because of their sensitivity to other forms of antibody therapy, and the extent to which B-cells and T-cells communicate at the molecular level. BsAbs that recognize CD3 and a number of antigens on malignant B-cells have been shown in vitro to be capable of retargeting T-cells. In animal models of B-cell malignancy, bsAb can eliminate tumor loads that are resistant to unmodified monoclonal antibody therapy. Ongoing early clinical trials in advanced B-cell lymphoma indicate CD3-based bsAbs have significant biologic effects, and suggest they have anti-tumor activity as well. A number of significant questions relating to bsAb therapy of B-cell malignancies remain. It is unclear what role both endogenously produced and exogenously administered cytokines are likely to play. Further exploration of whether bsAb can induce T-cells to target to tumor will also be required before the true promise of this novel form of immunotherapy can be determined.
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PMID:Bispecific monoclonal antibody therapy of B-cell malignancy. 771 27

Although gamma delta T cells have been postulated to act as a surveillance mechanism that eliminates transformed or otherwise damaged cells, little is known about tumor recognition by gamma delta T cells, including the Ags that are recognized and the molecules that present them. Previously, we described human gamma delta CTL that recognize the autologous B cell lymphoma. Here we report that these gamma delta CTL lyse heterologous cells transfected with the tumor Ig lambda chain gene. Furthermore, the lambda chain is recognized as processed peptide in an Id-specific manner. T cell recognition does not involve classical MHC molecules, but it could be blocked by Abs directed against the heat shock protein grp75. These findings show a specific gamma delta T cell response to a highly polymorphic Ag such as tumor Id and implicate heat shock protein as a molecule required for recognition.
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PMID:Gamma delta T cell recognition of tumor Ig peptide. 783 46

Mixed isotype MHC class II molecules (E alpha dA beta d) occur at extremely low levels on the surface of normal mouse B cells and macrophages, as determined by surface staining with an E alpha dA beta d-specific hamster mAb, H71-258.41. The surface levels of mixed isotype on the B cell lymphoma line A20 are approximately 1 to 2% that of surface I-A, whereas the levels of these molecules on normal mouse B cells were estimated to be at least two to four times less than those on A20. Nevertheless, other investigators have recently reported that immunization of normal H-2d mice with the sperm whale myoglobin peptide 110-121 (SWM(110-121)) elicits T cells, predominantly, V beta 8.2+, that recognize the peptide only in context of E alpha A beta. We have characterized a large number of SWM(110-121)-specific T cell hybridomas from several strains of H-2d haplotype mice. All of the V beta 8.2+ 110-121-specific hybridomas were found to be restricted by E alpha dA beta d, whereas, of the V beta 8.2- 110-121-specific group, approximately half recognized the peptide through E alpha dA beta d whereas the remainder were restricted by either I-Ad or I-Ed. mAb inhibition experiments revealed that 14-4-4S (E alpha-specific) could block presentation by mixed isotype completely, while MK-D6 (A beta d-specific) and H71-258.41 (E alpha dA beta d-specific) only inhibited presentation when the concentration of peptide was limiting. Although A20 expresses very low levels of mixed isotype, 10 to 100 nmol of the peptide produced a detectable response, illustrating the remarkable efficiency in presenting this peptide through E alpha dA beta d. The ability of normal mouse APC to use this restriction element despite its extremely low expression has important implications for the activation of T cells by low levels of peptide-MHC complexes.
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PMID:Expression and function of mixed isotype MHC class II molecules in normal mice. 825 92


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