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)

The plasminogen activator (PA) activity in various cell lines is suppressed by glucocorticoids. These phenomena are attributed to either a suppression of PA biosynthesis, to an increase of PA inhibitor or to a combination of both. The regulation of urokinase (UK) production in a human pre-B cell lymphoma line, RC-K8, by dexamethasone (Dex) and phorbol myristate acetate (PMA) was investigated. RC-K8 is a cell line which is consistently producing a high molecular weight UK in the conditioned medium (Kubonishi, I., et al: Jpn. J. Cancer Res. 76, 12-15, 1985). The cells were cultured in RPMI-1640 with Dex or PMA for 1-4 days. UK activity was measured using a chromogenic substrate S-2444 and the antigen by an ELISA kit. PAI-1 and PAI-2 antigens were also measured by ELISA kits and the complex between PA and PAI was examined by SDS-PAGE fibrin-zymography. The UK secretion in RC-K8 cells was inhibited by cycloheximide and actinomycin D. PMA at 0.16-1.6 uM up-regulated the UK activity approximately two-fold, parallel with the antigen, whereas Dex at 1-10 uM decreased the UK expression approximately half. These were verified by SDS-PAGE fibrin-zymography. Neither PAI-1, PAI-2 nor PA/PAI complex was detected in the conditioned medium and in the cell lysate. These data suggest that PMA up-regulates the UK secretion without inducing PAIs and the down-regulation of the UK secretion by Dex results from the inhibition of the expression of UK itself but not from the induction of PAIs.
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PMID:Down-regulation of urokinase secretion from a human lymphoma cell line RC-K8 by dexamethasone without inducing plasminogen activator inhibitors. 163 98

B29 is a B-lineage-specific gene predicted from sequence information to be a transmembrane member of the immunoglobulin (Ig) superfamily, with a single extracellular Ig-like domain. Its presumptive cytoplasmic region contains a peptide motif present in CD3 and other molecules involved in lymphocyte activation. Affinity-purified goat antibodies were prepared to a TrpE fusion protein of B29 and used to study B29 expression on lymphoid cells. The antiserum precipitated surface-labeled heterodimers from B lymphoma cells. One was 65-88 kDa (unreduced) or 36-47 plus 32-34 kDa (reduced) by SDS/PAGE analysis, regardless of detergent. A smaller heterodimer was detected only with Triton detergent extraction. IgM molecules were coprecipitated by the B29 antiserum when the weak detergent digitonin was used. In addition, cocapping experiments revealed that most B29 molecules codistribute with Ig on the cell surface. Although early B-lineage cells and plasma cells contain B29 mRNA, surface expression was detectable only on B cells that had significant amounts of surface Ig. The surface expression was B-lineage-specific and included cells from mutant xid mice and B-cell lines representing mu, delta, gamma, and alpha heavy-chain isotypes and both kappa and lambda light-chain types. The density of surface B29 protein correlated directly with surface mu heavy-chain density on subclones of a B-cell lymphoma and lipopolysaccharide-stimulated pre-B cells. These findings show that B29 is covalently linked in a heterodimer and are consistent with a recently proposed model of surface Ig complexes.
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PMID:B29 gene products complex with immunoglobulins on B lymphocytes. 173 34

The Ia+ B cell lymphoma, AKTB-1b, fails to stimulate thymic lymphocytes in a one-way mixed lymphocyte reaction unless pretreated with sialidase or inhibitors of N-linked oligosaccharide processing. A comparison of different sialidases and sialyltransferases suggests that the removal of only a subset of total surface sialic acid, rather than net desialylation of the cell surface, is required. Three sialidases were compared, including Vibrio cholerae (VC) and Clostridium perfringens (CP), which will cleave alpha 2-3, alpha 2-6, and alpha 2-8, sialic acid linkages, and Newcastle Disease virus (NDV), which will remove only alpha 2-3 and alpha 2-8 linked sialic acid. When treated with equivalent units of sialidase, CP-, VC-, and NDV-treated cells were 24-fold, sixfold, and threefold better stimulators than untreated cells. In contrast, VC released 1.3-fold and 2.5-fold more sialic acid per cell than did CP or NDV, respectively. Furthermore, VC was superior in reducing the levels of binding of the sialic acid-specific lectin, Limulus polyphemus agglutinin, in exposing Gal beta 1-3GalNAc and Gal beta 1-4GlcNAc residues, and in desialylating gangliosides. Two-dimensional gel analysis indicated that VC and CP were both equal and superior to NDV in the desialylation of iodinatable cell-surface proteins, including H-2Kk, I-A beta k, and a highly sialylated 65,000 dalton protein of unknown identity. Maximal resialylation of CP-treated cells with exogenously added CMP-NANA and either the alpha 2-3(Gal beta 1-3GalNAc) or alpha 2-6(Gal beta 1-4GlcNAc) sialyltransferase did not reduce the stimulatory capacity of these cells. However, resialylation of VC-treated cells with just CMP-NANA alone resulted in 49% reversal of their stimulatory capacity, and no additional reversal could be achieved with either of the sialyltransferases. Although the alpha 2-6(Gal beta 1-4GlcNAc) sialyltransferase was capable of adding back approximately 10% of the sialic acid removed, the endogenous activity added back approximately 0.1% of the total sialic acid removed. SDS-PAGE gels of the sialylated cells indicated that the exogenously added sialyltransferase labeled many different proteins, whereas the endogenous activity labeled far fewer proteins, predominantly in 46,000 and 25,000 m.w. range. Both the desialylation and resialylation data suggest that the sialidase-dependent stimulation is due to the desialylation of specific membrane structures. Together with previous studies, these data suggest that the sialic acids involved are probably alpha 2-6 linked to N-linked glycosyl moieties.
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PMID:Cell surface sialic acid influences tumor cell recognition in the mixed lymphocyte reaction. 295 14

The ability of an Ia+ B cell lymphoma, AKTB-1b, to stimulate thymocytes in the allogeneic mixed lymphocyte reaction is dependent on its prior treatment with either swainsonine or deoxynojirimycin, two inhibitors of the processing of asparagine-linked oligosaccharides. In the absence of drug treatment, the tumor cells fail to stimulate thymocytes, whereas pretreatment of the tumor cells with either drug results in a five- to 10-fold increase in their ability to induce thymocyte proliferation. Drug-treated AKTB-1b stimulates thymocytes at levels comparable to those obtained with allogeneic splenocytes. In contrast, the untreated lymphoma does stimulate splenic lymphocytes, and pretreatment with either inhibitor only marginally increases the response. Genetic studies demonstrate that the thymocyte response is still H-2 locus restricted and can be blocked by monoclonal antibodies against two tumor cell major histocompatibility antigens, H-2K and I-A. Drug treatment does not change cell surface I-A expression, and H-2K levels are apparently decreased one-third by deoxynojirimycin but are not affected by swainsonine. To verify that the drug protocol used was capable of altering the glycoconjugates of membrane-associated proteins, the endo-beta-N-acetylglucosaminidase H (endo H)-sensitivity of immunopurified H-2K and I-A was analyzed by SDS-PAGE. These studies demonstrated that swainsonine treatment does result in cell surface expression of glycoconjugates with altered oligosaccharide moieties. Likewise, deoxynojirimycin treatment results in the cell surface expression of an I-A alpha polypeptide with altered oligosaccharide chains while only marginally affecting H-2K and not affecting the I-A beta chain. An intracellular form of the I-A beta chain sensitive to endo H digestion in the presence of deoxynojirimycin is not detectable at the cell surface. Neuraminidase-digested AKTB-1b are also capable of stimulating allogeneic thymocytes. These studies demonstrate that changes in the glycosylation state of the tumor cell can markedly influence its recognition by allogeneic lymphocytes, and further, that different T cell populations differ in their response to such changes.
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PMID:Influence of asparagine-linked oligosaccharides on tumor cell recognition in the mixed lymphocyte reaction. 315 9

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

Monoclonal and polyclonal antibodies to the variable portions of antigen receptors (anti-idiotypes and anti-idiotopes) are often employed to study the molecular nature and the biological role of these antigen receptors. Such antibodies are operationally defined as those antibodies which bind to a particular immunoglobulin but not to other immunoglobulins of the same class in a radioimmunoassay or ELISA. The monoclonal antibodies 32D1 and 31D1 were initially defined as anti-idiotypic as they recognized an immunoglobulin preparation from the murine B cell lymphoma BCL1, but not other immunoglobulins of the same isotype as assessed by a radioimmunoassay. A potential artifact in defining anti-idiotypic antibodies in this way is the possibility of copurification of antigen and antibody, resulting in the tentative identification of anti-antigen as anti-idiotype. Previous studies have demonstrated that BCL1-IgM is involved in binding of murine leukemia virus (MuLV), and BCL1 immunoglobulin and MuLV-gp70 apparently co-purified as an immune complex. Disruption of the immune complexes with SDS and sucrose gradient purification of the immunoglobulin was adequate to prepare BCL1 immunoglobulin free of gp70 as assessed by radioimmunoassay with the monoclonal anti-gp70 RA3-4A3. This preparation of immunoglobulin was used to show that 31D1 does not bind to BCL1 immunoglobulin, but to the contaminating gp70 in the BCL1 immunoglobulin preparation. However, MAb 32D1 was definitively proven to be anti-idiotypic as it recognized SDS sucrose density gradient purified IgM and immunoisolated heavy chain and light chain from BCL1 immunoglobulin. Several other lymphomas were recognized by mAb 32D1, including the T cell lymphoma UNC1 and the B cell lymphoma Balenlm17. To determine whether mAb 32D1 recognized immunospecific receptors on these lymphoma cell lines immunoprecipitation studies were performed. Immunoisolation and molecular analysis revealed that mAb 32D1 did not recognize the antigen receptor on these two cells, but instead recognized a cell-specific gp70. This observation demonstrates that monoclonal antibodies to known antigens (in this case an anti-idiotype) can crossreact with apparently unrelated molecules. The potential significance of this cross reaction to the antigens recognized by B cell lymphomas is discussed.
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PMID:Molecules recognized by anti-idiotypic monoclonal antibodies to the B cell lymphoma, BCL1. 350 25

A natural N-linked glycosylation site (Asn-Val-Thr) at amino acid positions 18-20 (Kabat's numbering) was identified in the framework-1 (FR-1) region of the light chain variable (V kappa) domain of a murine anti-B cell lymphoma Ab, LL-2. Our earlier studies demonstrated that no contact between the V kappa-appended oligosaccharide and the Ag binding site was evident, because glycosylation at this site did not affect the Ag binding property of the Ab. By using the murine LL-2 F(ab')2 fragment (which is devoid of constant region-appended oligosaccharide) as substrate, as much as five bifunctional chelator molecules per F(ab')2 fragment could be site specifically conjugated at the V kappa-appended carbohydrate moiety with no reduction in immunoreactivity. The resulting conjugates labeled efficiently with both 90Y and 111In, with no significant effect on Ab affinity. In contrast, conjugation of less than five chelates/Ab fragment randomly at lysine residues resulted in a three- to fivefold reduction in affinity. By a single Arg to Asn mutation, an N-linked glycosylation site similar to that of LL-2 was introduced in the FR-1 segment of a nonglycosylated, humanized anti-carcinoembryonic Ag (CEA) Ab, MN-14 (hMN-14). Glycosylation at the engineered carbohydrate-addition site was demonstrated by SDS-PAGE analysis. Neither glycosylation nor site-specific conjugation of chelate at the V kappa-appended carbohydrate moiety resulted in the loss of immunoreactivity. The glycosylated hMN-14 conjugate labeled efficiently with 90Y.
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PMID:Engineering a unique glycosylation site for site-specific conjugation of haptens to antibody fragments. 775 35

The successful clinical experience with antibody LL2 (an IgG2a, anti-B-cell lymphoma antibody) in radioimmunodetection and radioimmunotherapy suggests that this antibody may have potential as a carrier of cytotoxic agents. The internalization, cellular trafficking, and catabolism of this antibody in target human Burkitt lymphoma cells (Raji) were investigated. Internalization of intact antibody as well as of the F(ab')2 and Fab' fragments was detected by an FITC-labeled anti-mouse second antibody probe, and evaluated by fluorescence microscopy. Internalization of intact IgG (or the fragments) was observed as early as 5 min after incubation at 37 degrees C. Initially, the internalized antibodies were present as micro-particles inside the cell membrane, and were translocated to the lysosomal compartment within 2 hr. The anatomic location of the internalized antibody, before translocation to the lysosomal compartment, was deduced by comparing the fluorescence images obtained with the antibody to those obtained with fluorescent probes with known cellular distribution in a co-internalization study. A Golgi-like compartment was found to be involved in the translocation of the antibody. Cellular catabolism of the bound antibody was studied by using 125I-labeled antibody on the target cells. At 21 h, 40% of the radioactivity was released into the supernatant as degraded fragments. The observation suggested that the antibody was degraded mainly in the lysosomes, since the degradation was significantly inhibited in the presence of lysosomal inhibitors such as ammonium chloride or leupeptin. Subcellular fractionation of Raji cells after the binding of 125I-labeled LL2 indicated that the antibody was translocated to lysosomes as evidenced by SDS-PAGE. The rate of internalization (Ke) of LL2, and the re-expression of the antigen were determined. The rapid internalization of LL2 and the re-expression of the antigen suggest that this antibody may have potential as a therapeutic immunoconjugate, since it could deliver a higher accumulation of cytotoxic agents into lymphoma cells.
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PMID:Internalization and intracellular processing of an anti-B-cell lymphoma monoclonal antibody, LL2. 811 89

WEHI-231 is a murine B cell lymphoma that has been used extensively as a model for the immature stage B cell and its functional response to Ag receptor cross-linking as a model for immature B cell tolerance. This cell line expresses sIgM, CD5, and FcR gamma, but lacks the B cell-specific isoform of CD45 (B220). This study demonstrates for the first time that WEHI-231, in contrast to classically defined immature B cells, expresses delta on its surface. Analysis of delta on WEHI-231 revealed structural differences with respect to that on BAL-17 or primary splenic B cells. Although the m.w. of delta on the latter two B cell populations was similar, delta on WEHI-231 manifested a marked increase in its apparent m.w. deduced by SDS-PAGE. This difference was found to be due primarily to differential N-linked glycosylation. Signal transduction through the endogenous sIgD on WEHI-231 was investigated. In contrast to cross-linking of sIgM, cross-linking of the endogenous surface IgD on WEHI-231 was unable to generate a negative growth response in these cells. This inability may be due to uncoupling from normal surface Ig signaling pathways. The signaling properties of the endogenous sIgD on WEHI-231 differ from that on primary B cells and other sIgD-expressing cell lines. Whereas sIgD on splenic B lymphocytes or the mature B cell line BAL-17 is coupled to inositol phospholipid hydrolysis and calcium mobilization, cross-linking of sIgD on WEHI-231 failed to elicit these events, although induced changes in tyrosine phosphorylation were observed. Thus, endogenous expression of surface IgD on WEHI-231 is inconsistent with its representing the classically defined immature stage B cell. The structural and signaling differences associated with delta on these cells suggest the potential for developmentally regulated delta function and model for study of sIgD signal transduction.
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PMID:Endogenous expression of delta on the surface of WEHI-231. Characterization of its expression and signaling properties. 840 28

Annexin II is a growth-regulated gene, whose expression is significantly increased in various human cancers. We examined annexin II expression in II human B-cell lymphoma cell lines and in normal B-cells. Wide variation was observed in the levels of annexin II in these cell lines. Annexin II overexpression was observed in 5 cell lines, while significantly reduced expression was observed in Raji, OMA-BL-1 and REH cell lines. Analysis of the annexin II gene, mRNA and protein in Raji and OMA-BL-1 cell lines indicated that annexin II gene was unaltered and that a low level of annexin II transcripts are produced in these cells. Down-regulation of annexin II expression was at the transcriptional level, and no reexpression of annexin II was observed after treatment of cells with demethylating agents. Thus methylation of the annexin II gene does not appear to be responsible for annexin II down-regulation. A slow migrating altered form of annexin II was detected in Raji and OMA-BL-1 cells, which was detected with the anti-chicken annexin II antiserum, but not with the anti-human annexin II antiserum. The slow migrating annexin II species was found to be sensitive to dephosphorylation by calf intestinal alkaline phosphatase, resulting in reduction of the size of the protein on SDS-polyacrylamide gels. The phosphorylated annexin II was also observed in nuclear extracts of human K562 and HeLa cells. Thus, Raji and OMA-BL-1 cells exclusively produce a phosphorylated form of annexin II, and phosphorylated annexin II may be important for cell survival and proliferation.
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PMID:Altered expression of annexin II in human B-cell lymphoma cell lines. 889 68


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