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 BALB/c-derived mouse B cell lymphoma line, 2PK3, expresses mixed isotype E alpha dA beta d and classical I-E class II molecules on its surface, but normal surface I-A expression is not detectable. Northern blot analysis showed comparable amounts of A alpha mRNA in 2PK3 as compared to another Iad expressing B cell lymphoma, A20, which predominantly expresses I-A and I-E. Sequence analysis of 2PK3 A alpha cDNA revealed a single nucleotide difference in the signal sequence that would result in a proline for leucine substitution at position - 12. In vitro translation of 2PK3 A alpha mRNA gave results suggesting that the signal peptide mutation prevented translocation of the A alpha protein across the rough endoplasmic reticulum which would provide an explanation for the lack of I-A expression in 2PK3. I-A expression was restored by transfecting a functional A alpha d gene into 2PK3. Although I-A was expressed at high levels in some transfectants, in all cases significant levels of mixed isotype were still detected. Functional studies performed using antigen-specific I-A(d)-restricted and E alpha d-A beta d-specific T cell hybridomas confirmed the levels of expression of I-A(d) and E alpha dA beta d respectively on the transfectants and showed that these molecules were functional. An interesting observation from this study is the continued expression of significant levels of E alpha dA beta d in spite of competition from restored expression of I-A(d).
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PMID:Characterization of defective I-A surface expression in a mixed isotype expressing murine B cell lymphoma: continued expression of E alpha d A beta d despite competition from restored A alpha d A beta d pairs. 132 33

In the A20/2J BALB/c B cell lymphoma, Southern analysis revealed an insertion of approximately 6 kilobases of DNA into the first intron of one Ebd-allele. Two observations suggest that the rearrangement did not occur recently in the A20/2J subline. Firstly, normal and altered Ebd-alleles are present in equal numbers, and secondly, the LB 27.4 and LS 102.9 somatic cell hybrids formed at an earlier date both possess the rearrangement. Sequences of two cDNA clones, lambda Eb-7 and lambda Eb-125, selected from an A20/2J cDNA library prepared from poly [A+] RNA indicate that the rearranged Ebd-allele directs the synthesis of atypical Eb transcripts. The clones contain Eb sequence linked to a portion of retroviral-like intracisternal A-particle (IAP) genomic sequence, and they appear to be copies of mRNA produced by splicing between a 5' donor site in the retroviral transcript and the 3' acceptor site of the Eb gene's first intron. The longer lambda Eb-125 insert corresponds to RNA that initiated in the 5'-untranslated region of the Eb gene. The 3'-end of the first Eb exon joins to long terminal repeat sequence, and retroviral sequence extends up to the splice junction with the second Eb exon; 3' of the junction, the lambda Eb-125 sequence corresponds to that of a correctly spliced Eb transcript. It seems feasible that the cDNA clones represent hybrid RNA synthesized by read-through transcription of the Eb coding region and an IAP element inserted into the first intron of the rearranged Ebd-allele.
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PMID:Interaction of H-2Eb with an IAP retrotransposon in the A20/2J B cell lymphoma. 135 78

Clinical data have suggested that graft-versus-host disease (GVHD) plays a crucial role in the antileukemic effects of bone marrow grafts. We investigated (a) whether bone marrow cells unable to induce GVHD can effect graft-versus-leukemia (GVL) activity and (b) whether such antileukemic capacity depends on the presence of T lymphocytes in the graft. Balb/c mice were inoculated with A20 cells, a B-cell lymphoma/leukemia of Balb/c origin. Four weeks after tumor inoculation the animals were lethally irradiated and received a bone marrow graft. Cells from (Balb/c x C57) F1 or (C3H x Balb/c) F1 hybrids were transplanted into parental-strain Balb/c mice. Since lymphocytes from F1 hybrids are unable to cause graft-versus-host reactivity against a parental-strain animal, we used this experimental setting to explore GVL effects in a GVHD-free system. In vitro incubation with monoclonal anti-Thy-1.2 antibody plus complement was used to eliminate Thy-1+ cells. After syngeneic transplantation, the death rate due to leukemia remained unchanged (91%) compared with that among untreated animals (86%). Following transplantation of F1 marrow cells of either (C57 x Balb/c) F1 or (C3H x Balb/c) F1 origin, death rates of 40% and 50% were observed; these were significantly lower. Depletion of Thy 1+ cells from bone marrow graft caused only a slight increase in the leukemic death rate after transplantation of bone marrow of (C57 x Balb/c) F1 hybrid origin (50%), but a high leukemic death rate was seen after transplantation of (C3H x Balb/c) F1 bone marrow (100%). Additional experiments with fully allogeneic, T-cell-depleted C57 bone marrow transplantation suggest an antileukemic effect that is comparable to that seen after transplantation of unmanipulated F1 bone marrow. Taken together, our results indicate that GVL activity can be dissociated from graft-versus-host reaction.
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PMID:Graft-versus-leukemia activity after bone marrow transplantation does not require graft-versus-host disease. 163 77

We have compared the functional properties of I-Ad expressed on different cell types. Specifically, we have transfected I-A alpha d and I-A beta d cDNA into a panel of T cell thymomas of various phenotypes. Excellent class II surface expression was achieved in all T cell tumors, equivalent in level to that found on the B cell lymphoma A20. Interestingly, however, two allo-I-Ad-specific Thy differed in their recognition of the transfected tumor cells: whereas the 42H11 T cell hybridoma (THy) was stimulated very efficiently by all transfectants, the RK38.2.2 Thy did not react to any of them. Both THy responded equally well to I-Ad on A20 B lymphoma cells. Purified macrophages isolated from various sources were also differentially recognized by the two THy, although there was only a quantitative difference in stimulation. Taken together, these results are best interpreted to show that the TCR of the RK38.2.2 THy is specific for I-Ad in the context of a B cell-specific determinant, possibly a self-peptide that is naturally associated with Ia. A cross-reactive molecule could be expressed by macrophages and COS-1 cells, but not by T cells.
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PMID:The expression of a tissue-specific self-peptide is required for allo-recognition. 196 23

The B lymphoblastoid cell line clone 13 (a subclone of the mutant cell line P3JHR-1) has been found to express high levels of HLA-DQ; by contrast, HLA-DR and -DP antigens are not expressed and cannot be induced by interferon gamma. Northern blot analysis using gene-specific probes indicated that the lack of surface expression of the DR and DP antigens is due to a marked decrease in the levels of steady-state RNA for both the alpha and beta chains. Southern blots demonstrated that none of the transcriptionally repressed genes are grossly deleted. Preparations of interspecific transient heterokaryons between clone 13 and the class II antigen-positive murine B cell lymphoma, A20, resulted in reactivation of the DRA gene and surface expression of both the DR and DP molecules. The efficiency of the DRA promoter relative to the DQB promoter is markedly and specifically diminished in clone 13 (P3JHR-1) as compared with the parental cell line, Jijoye, as assayed both by transient expression of appropriate chloramphenicol acetyltransferase gene (CAT) constructs and by in vitro transcription analysis. These data clearly demonstrate the existence of an isotype-specific trans-acting factor, and provide direct evidence that the highly homologous class II genes have distinct regulatory mechanisms.
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PMID:An isotype-specific trans-acting factor is defective in a mutant B cell line that expresses HLA-DQ, but not -DR or -DP. 199 50

Membrane-bound immunoglobulin (mIg) is the antigen receptor on B lymphocytes mediating early events in antigen presentation and signal transduction. Wild-type human mIgM constructs transfected into the murine B-cell lymphoma A20 are expressed as transmembrane proteins with antigen presentation and signaling functions comparable to the endogenous mIgG2A; the transfected wild-type mIgM is internalized rapidly after anti-Ig cross-linking. Transfected constructs lacking the normal three-amino acid cytoplasmic tail are expressed exclusively as phosphatidylinositol-linked proteins, lack both antigen presentation and signal transduction functions, and are internalized slowly following anti-Ig binding. The molecular mass of the cytoplasmic tail-deleted phosphatidylinositol-linked Ig molecule is consistent with cleavage of the transmembrane residues during processing. Cytoplasmic domains may therefore regulate the mode of expression of membrane proteins and thereby influence their functional capabilities.
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PMID:Cytoplasmic tail deletion converts membrane immunoglobulin to a phosphatidylinositol-linked form lacking signaling and efficient antigen internalization functions. 202 99

Murine Ly1+ pre-B cell lines, including 70Z/3 and three pre-B cell lines derived from long-term bone marrow cultures, exhibited selective adherence to bone marrow stromal cells. In contrast, splenic B cells, the A20 B-cell lymphoma, and four Ly1- B cell lines derived from long-term bone marrow cultures failed to adhere substiantially to bone marrow cultures failed to adhere substiantially to bone marrow stroma. Ly1+ pre-B cell lines were induced to express kappa light chains by exposure to either lipopolysaccharide (LPS), recombinant interleukin-1 (IL-1), or stromal cells. However, induction of kappa light chains failed to prevent pre-B cell adherence to stromal cells. Supernatants derived from primary bone marrow stromal cells decreased Ly1 expression on the Ly1+ pre-B cell lines. These experiments suggest that (1) expression of immunoglobulin light chains by developing Ly1+ pre-B cells is mediated by bone marrow stromal cells; (2) loss of specific adherence to stroma is progressive and occurs post-light chain induction; and (3) soluble products of stromal cells may downregulate expression of surface Ly1 on otherwise Ly1+ pre-B cells. The importance of these observations to the development of both the Ly1- and Ly1+ B cell lineages in the mouse is discussed.
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PMID:Bone marrow stromal cells modulate both kappa light chain and Ly1 antigen expression on Ly1+ pre-B cell lines in vitro. 211 35

Ia antigen is a receptor for the superantigen staphylococcal enterotoxin A (SEA). Peptides I-A beta b(30-60), I-A beta b(50-70), I-A beta b(65-85), and I-A beta b(80-100) of the MHC class II antigen beta chain on mouse (H-2b) accessory cells were synthesized. Only I-A beta b(65-85) inhibited SEA binding to the mouse B-cell lymphoma line, A20 (H-2d) and the human Burkitt's lymphoma line, Raji (HLA-DR). The I-A beta b(65-85) sequence is a predicted alpha-helix along the hypothetical antigen binding cleft of the Ia molecule. I-A beta b(65-85) also directly and specifically bound both the intact SEA molecule and its Ia binding site, represented by the peptide SEA(1-45). The results suggest that I-A beta b region (65-85) is a necessary site for Ia molecular interaction with the superantigen SEA. Further, the data suggest that the same helical region of other Ia antigens binds SEA irrespective of haplotype and species.
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PMID:The I-A beta b region (65-85) is a binding site for the superantigen, staphylococcal enterotoxin A. 215 98

Mouse class II major histocompatibility complex genes have been shown to be regulated at the level of transcription for both tissue-specific and inducible expression. In particular, IFN-gamma induction of the class II genes has been shown to occur at the transcriptional level, although the role that additional post-transcriptional mechanisms of regulation may play in this induction is not known. To evaluate IFN-gamma effects on transcriptional and post-transcriptional events of class II gene expression, we examined the rate of decline of class II transcription, steady-state mRNA, and cell surface protein following the removal of IFN-gamma from maximally stimulated WEHI-3 cells (an IFN-gamma inducible, myelomonocytic cell line). We determined that transcription of class II genes almost completely returned to baseline levels eight hours after removal of IFN-gamma. However, the steady-state level of class II mRNA's required 4 days, and membrane Ia expression required 5 days to return to baseline levels. This decay was linear and allowed us to determine a half-life value of 16-20 h for class II transcripts. These data demonstrate that, following removal of IFN-gamma from fully stimulated cells, transcription of the class II genes declined rapidly, but mRNA was quite long-lived. We also assessed the class II mRNA stability in unstimulated WEHI-3 cells and the B-cell lymphoma. A20/2J, by actinomycin D treatment and northern blot analysis. In agreement with the IFN-gamma washout experiments, transcripts from all four class II genes were quite long-lived in these cell types, with a half-life greater than ten hours. These data support the concept that IFN-gamma acts primarily at the level of class II transcription and argues against IFN-gamma playing a major role in post-transcriptional modulation of class II expression.
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PMID:Evidence that IFN-gamma does not affect MHC class II gene expression at the post-transcriptional level in a mouse macrophage cell line. 250 46

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.
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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


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