UMLS:C0079731 - FACTA Search

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

We investigated the anti-tumor effects of recombinant mouse interleukin (IL)-4 and IL-5 by using a transplantable B cell lymphoma 38C13 cell line as a model. Daily local administration of either IL-4 or IL-5 produced moderate but significant inhibition of the rate of local tumor growth and prolongation of mean survival time (MST) in syngeneic C3H/HeJ mice; these anti-tumor effects appeared to plateau at low doses. Histopathologic and immuno-histochemical examination revealed necrotic changes in the cytokine-treated tumors, associated with infiltration of inflammatory cells such as eosinophils, macrophages, and lymphocytes. The infiltrating lymphocytes were found to be Thy-1.2+ T cells. To elucidate the importance of T cells, the rate of tumor growth and the MSTs were compared between athymic T cell-deficient BALB/c nude mice and immunocompetent C3H/HeJ mice. In the nude mice the transplanted tumor grew more rapidly and the MST was shorter than in the normal mice, suggesting a significant contribution of infiltrating T cells in the anti-tumor effects of the interleukins. Lastly, in vitro, growth inhibition of the 38C13 cells was observed in a dose-dependent manner at relatively high concentrations of either cytokine. Therefore, we conclude that both IL-4 and IL-5 have moderate anti-tumor effects against 38C13 B cell lymphoma both in vivo and in vitro, and that the observed in vivo anti-tumor effects are probably mediated both by tumoristatic action of infiltrating cells, such as eosinophils, macrophages and T lymphocytes, and by direct anti-proliferative action of the recombinant cytokines.
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PMID:Anti-tumor effects of interleukin-4 and interleukin-5 against mouse B cell lymphoma and possible mechanisms of their action. 155 1

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

Rat liver beta-galactoside alpha-2,6-sialyltransferase and Vibrio cholerae sialidase were used with cytidine-5'-monophospho-N-acetyl-[3H]neuraminic acid (CMP-[3H]NeuAc) to specifically probe the distribution and sialylation state of Gal beta 1-4GlcNAc residues on N-linked saccharides on the surfaces of murine lymphocytes. The relative extent of exogenous sialyltransferase-mediated sialylation (per cellular protein) was thymocytes greater than T-cells greater than T-cell lymphoma (EL-4) greater than B-cells greater than B-cell lymphoma (AKTB-1b) greater than splenocytes. Prior desialylation increased exogenous resialylation by 23.8-, 13.1-, 7.1-, 7.9-, 7.0-, and 5.3-fold for splenocytes, B-cells, T-cells, EL-4, AKTB-1b, and thymocytes, respectively. Though numerous glycoproteins were labeled, the majority of the Gal beta 1-4GlcNAc residues were detected on a relatively small number of cell surface proteins, many of which are well-defined lymphocyte antigens. Gal beta 1-4GlcNAc residues on thymocytes were found to exist in an undersialylated state on T200 but not on other antigens (e.g., Thy-1). T200 was found to be fully sialylated on mature cells (i.e., hydrocortisone-resistant thymocytes and splenic T-cells), suggesting that its sialylation state is developmentally regulated. These studies indicate that the number, sialylation state, and polypeptide distribution of the penultimate structure, Gal beta 1-4GlcNAc, differ on N-linked saccharides on the surfaces of different lymphocyte populations.
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PMID:Surfaces of murine lymphocyte subsets differ in sialylation states and antigen distribution of a major N-linked penultimate saccharide structure. 213 33

The expression of cell surface antigens recognized by UB-12 monoclonal antibody against rat hemopoietic cells was examined in fetal liver, and adult bone marrow using immunohistochemistry, radioimmunoassay, and flow cytofluorometry. Comparisons were made with the expression of the antigens recognized by OX-7 (anti-Thy-1) or W3/13 (anti-leukocyte sialoglycoprotein) antibodies. UB-12 positive cells appeared at earlier stages of gestation and in higher cell frequency than OX-7 or W3/13 positive cells in fetal liver. The antigen detected with UB-12 antibody was positive in fetal liver at day 12 and increased at day 15, reaching about 90% of the positive cells. In bone marrows, UB-12 positive cells started to appear around birth and were about 30-40% of total nucleated cells during adult periods. Thus, the antigen recognized by UB-12 was found only during early stages of blood cells. UB-12 monoclonal antibody recognized a B-cell lymphoma, Y-3, but did not react with a rat T lymphoma cell line. This monoclonal antibody may be important for distinguishing normal and neoplastic B cells and their precursors.
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PMID:Analysis of hemopoietic cells in rat bone marrow and fetal liver with monoclonal antibody. 233 52

In somatic cell hybrids between the pseudodiploid Thy-1- Abelson-leukemia-virus-induced pre-B cell lymphoma RAW 253.1 and the Thy-1+ T-cell lymphoma, AKR1 (Thy-1+), all cells express the Thy-1 allele of the T-cell parent but most hybrid cells do not express the Thy-1 allele of the pre-B cell lymphoma parent. The Thy-1 allele of the pre-B cell parent, however, is spontaneously activated in a minor proportion of hybrid cells. By sorting for cells expressing the Thy-1 allele of the pre-B cell parent, derivative clones in which 100% of cells express both parental Thy-1 alleles can be isolated. Revertants with a phenotype identical with that of the original hybrid cell line can be isolated from these derivatives by sorting for nonexpression of the Thy-1 allele of the pre-B cell parent. These first-generation revertant cell lines have lost one copy of the Thy-1 gene derived from the pre-B cell lymphoma parent. By a further cycle of sorting, derivatives in which 100% of cells express both parental Thy-1 alleles can again be obtained. Second-generation revertants isolated by sorting these Thy-1+ hybrid cells for nonexpression of the Thy-1 allele of the pre-B cell parent no longer contain a normal copy of the pre-B cell Thy-1 allele and this surface antigen is no longer expressed by any cells in the population. These results are consistent with a mechanism that sequentially activates each copy of the Thy-1 gene derived from the pre-B cell lymphoma parent. Hybrids between the class D Thy-1- mutant, AKR1 (Thy-1- d), in which the 5' region of the Thy-1 structural gene has been deleted, and RAW 253.1 cannot be activated to express either Thy-1 allele. This result indicates that a sequence upstream of exon 2 of the active Thy-1 allele is critical for the initial activation event.
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PMID:Sequential activation and loss of the pre-B cell Thy-1 gene in T-cell X pre-B cell somatic hybrids. 289 32

The characterisation of a new murine B cell lymphoma, A31, is described. Histopathological examination of passaged tumour indicates that initial infiltration occurs in the spleen, lymph nodes, Peyer's patches and liver, while in the terminal phase the bone marrow, gonads and occasionally the central nervous system become involved. The terminal spread is coincidental with the leukaemic phase in the tumour. The tumour cells show typical B cell characteristics in vitro. These include surface immunoglobulin (Ig) of mu, kappa isotype, surface Ia, Thy-1 negativity and an increased uptake of tritiated thymidine following incubation with lipopolysaccharide. A31 cells secrete low levels of IgM into the tissue culture fluid. Short-term culture produced only 100 ng IgM per 10(7) cells over 8 h and no tumour-associated monoclonal band could be detected in the serum of tumour-bearing mice. Chromosomal karyotypes of A31 cells gave model numbers 2n=40 normal, and 2n=41, with partial trisomy of chromosome 2, and trisomy of 17. There was loss of a chromosome 6 and the Y chromosome, together with the translocation of part of an 11 to one of the two unidentified marker chromosomes. The responses of lymphoma-bearing mice to therapeutic levels of cyclophosphamide and vincristine sulphate and also to whole body X-radiation are illustrated. This tumour may help in unravelling the complex biology of B cell lymphoma and because of its low level of Ig secretion, be of particular value in experimental immunotherapy.
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PMID:Characterisation of a new murine B cell lymphoma. 349 18

CH12, a murine B cell lymphoma derived in B10 H-2aH-4bp/Wts mice after transfer of SRBC hyperimmunized spleen cells into an adult-thymectomized, sublethally irradiated, syngeneic recipient, is demonstrated to bear surface IgM specific for a determinant found on SRBC and ChRBC. The Ig specificity has been demonstrated by rosetting assays and complement-dependent hemolysis. The removal of CH12 surface IgM by capping with anti-mu or with anti-CH12 idiotype, but not with anti-gamma or with irrelevant anti-idiotype, eliminated the formation of rosettes between CH12 and SRBC or ChRBC. The absorption of CH12 Ig produced in vitro, with either SRBC or ChRBC but not with HRBC, removed all hemolysin activity against SRBC, demonstrating that only one CH12 product was responsible for the reactivity with both SRBC and ChRBC. CH12 has a surface phenotype of a relatively mature B cell expressing surface Ig (IgM-mu,kappa) and la antigens, but lacking Thy-1 or detectable Fc or C3 receptors. CH12 also expresses the antigen Lyt-1. Growth of CH12 in vivo or in vitro results in the generation of up to 3% direct PFC and serum hemolysin, which shows that CH12 is not irretrievably "frozen". The generation of PFC and serum hemolysin is associated with increased population density, and the rate of PFC and serum hemolysin accumulation cannot be explained by simple cell division. A continuously secreting hybridoma derived from CH12 was used to purify the CH12 IgM to facilitate studies of protein sequence and idiotype.
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PMID:Antigen-induced lymphomagenesis: identification of a murine B cell lymphoma with known antigen specificity. 619 26

We have previously described a murine B-cell lymphoma, CH12, the cells of which bear surface IgM reactive with sheep erythrocytes (SRbc) and which could differentiate to secrete hemolytic antibody. The question addressed in this paper was whether differentiation of CH12 cells could be influenced by interaction with regulatory T cells and antigen. If so, we wanted to know whether the conditions required differed from those known to govern similar interactions with normal B cells. We had two reasons for wanting to answer these questions. First, we wondered whether CH12 could be used as a clonal population of indicator cells to study the regulation of B cell differentiation and, second, we wanted to know the extent to which these neoplastic cells were still responsive to normal regulatory signals. The first addresses a major difficulty which must be faced in studies of normal B cell differentiation: to what extent is the interpretation limited by heterogeneity of the B cells used? The second relates to the nature of neoplasia and the possibility that neoplastic cells might be rendered harmless by inducing terminal differentiation. CH12 is one of a series of transplantable B cell lymphomas which arose in B10.H-2aH-4b p/Wts (2a4b) mice, following intense immunization with SRbc. It is a monoclonal tumor, all the cells of which bear membrane IgM(kappa) of a single idiotype, reactive with sheep and chicken Rbc and with bromelain-treated autologous mouse Rbc. The cells express KkAkEk and Dd antigens appropriate to the H-2a haplotype. During the latter stages of growth in vivo or in vitro, a small proportion (less than 3%) of the cells differentiate to secrete hemolytic antibody as measured by the Cunningham assay for plaque forming cells (PFC). We cultured CH12 cells for 3 or 4 days, together with antigen and spleen cells from primed animals, and assayed for PFC induction. Differentiation was induced by spleen cells from SRbc primed 2a4b mice in the presence of SRbc or ChRbc but not rabbit or human erythrocytes. Activity was depleted by treatment of the spleen cells with anti-Thy-1 or anti-Lyt-1 but not anti-Lyt-2 plus complement. Helper cells could also be induced by priming 2a4b mice with ChRbc but not rabbit or human Rbc. Neither of these last two would induce differentiation of CH12, even when both homologous antigen and SRbc were present in the cultures.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Induced differentiation of a B cell lymphoma with known antigen specificity. 624 57

The CD5+ B cell lymphoma clone, CH12.LX, endogenously produces IL-4. Blocking the binding of this IL-4 to its cellular receptor inhibited the continuous proliferation of CH12.LX. mAb specific for either IL-4 or the IL-4R profoundly and specifically inhibited the proliferation of CH12.LX cells in a concentration-dependent manner, within 4 h after the addition of mAb. The addition of exogenous rIL-4 alone to CH12.LX cells had no effect on either proliferation or antibody secretion. However, exogenous rIL-4 was able to counteract the effects of anti-IL-4 antibody. Treatment of CH12.LX cells with antisense RNA oligodeoxynucleotides to IL-4 also specifically inhibited cell proliferation and decreased the levels of IL-4 secreted into the culture supernatants by more than 50%, without effect on total RNA or protein synthesis. Effects of antisense IL-4 were also blocked by addition of exogenous IL-4. Control oligodeoxynucleotides of equal size and base composition had no effect, and IL-4 antisense oligodeoxynucleotides did not effect the growth of a B cell lymphoma clone which does not produce IL-4. Blocking the binding of endogenously produced IL-4 to CH12.LX cells did not change the levels of membrane IL-4R or CD5 molecules. However, the constitutive expression of Thy-1 by these B cells was markedly decreased, and anti-Thy-1 antibodies decreased proliferation and PMA-induced aggregation of CH12.LX cells. Autocrine secretion of IL-4 thus appears to be required both for the continuous proliferation of CH12.LX B cells, as well as their expression of Thy-1, which may function either as a homotypic adhesion molecule or a signal transduction molecule for these cells. These findings indicate that endogenously produced lymphokines may play a critical role in the maintenance of B cell hyperproliferative disorders.
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PMID:Endogenous secretion of IL-4 maintains growth and Thy-1 expression of a transformed B cell clone. 809 58

Despite improved procedures in chemotherapy and bone marrow transplantation (BMT), post-BMT leukemia relapse rates have remained rather constant in the last decade. Immunotherapy with monoclonal or bispecific antibodies (bsAb) is a promising approach to improve this situation, but is hampered by the absence of tumor-specific antigens on the majority of tumors. To evade this problem, we developed a new tumor-specific approach in which bispecific antibodies exploit chimerism after allogeneic BMT by redirecting donor T cells against recipient-specific antigens on tumor cells. Two different leukemia relapse models were established using a T-cell lymphoma (ST-1) and a B-cell lymphoma (BCL1) to evaluate the efficiency of such a therapy. In these experiments, irradiated BALB/c (Thy-1.2+, I-Ad) mice were transplanted with C57BL/6 Thy-1.1 (I-Ab) BM cells under the protection of graft-versus-host disease-preventing monoclonal antibodies. Forty-five days after BMT, the chimeric mice were injected with either 2 x 10(4) recipient-type, Thy-1.2+, CD3- ST-1 cells or major histocompatability complex (MHC) class II+ (I-Ad)-BCL1 cells. Four days later, the mice were treated with 8 microg bsAb G2 (anti-CD3 x anti-Thy-1.2) or 10 microg (+10 microg, day 6) bsAb BiC (anti-CD3 x anti-I-Ad), respectively. These combinations guaranteed exclusive binding of the bsAbs target arms to tumor cells, leaving the surrounding, donor-type hematopoietic cells unbound. Compared with the parental antibodies, the bsAbs markedly reduced tumor mortality. Between 34% and 83% of mice survived in the bsAb groups compared with 0% of the control groups treated with parental antibodies, clearly documenting the benefit of the redirection principle. Furthermore, cytokine release (interleukin-6) after anti-CD3 antibody or bsAb treatment was decreased by administering a low-dose antibody preinjection. We have shown (1) that 6 weeks after BMT, when donor T-cell reconstitution is still in progress, T-cell-redirecting bsAb are clearly superior to parental antibodies in terms of tumor cell elimination; and (2) that the polymorphism of a common antigen such as Thy-1 or a clinically more relevant target antigen such as MHC class II can be used as an operational tumor-specific antigen after allogeneic BMT.
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PMID:Bispecific antibodies target operationally tumor-specific antigens in two leukemia relapse models. 897 58

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