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

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.
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PMID:Production of multiple lymphokines by the A20.1 B cell lymphoma after cross-linking of membrane Ig by immobilized anti-Ig. 266 89

We have observed that a 2-h pretreatment of murine B cells with cholera toxin (CT) renders the B cell incapable of receiving an activation signal via surface Ig as measured by cell volume increase and entry into the S phase of the cell cycle. In contrast, CT pretreatment does not inhibit the delivery of a signal by IL-4, as measured by increase in cell volume. In fact, CT pretreated B cells are able to respond to anti-Ig in the presence of IL-4, as measured by both an increase in cell size and entry into S suggesting that IL-4 overcomes the effects of CT on normal B cell activation. Despite blocking the anti-Ig-mediated entry into the cell cycle, CT was not able to interfere with the induction of nonresponsiveness by anti-Ig in normal B cells or with the delivery of growth-inhibitory signal to the B cell lymphoma WEHI-231. These results suggest that there are two signaling pathways mediated by cross-linking of surface Ig: one pathway sensitive and the other insensitive to modulation by CT.
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PMID:Cholera toxin-sensitive and insensitive signaling via surface Ig. 278 8

Recently we described a murine T-cell hybrid that produces activities that promote the differentiation of eosinophils (eosinophil differentiation factor) and cause proliferation of the BCL1 B-cell lymphoma (B-cell growth factor II activity). Both activities appear to be associated with the same molecule, which has therefore been termed interleukin 4. The hybrid does not produce any other known lymphokines. We now find that purified interleukin 4 has no effects on small resting B cells but induces naturally occurring large B cells (which have presumably been preactivated in vivo) to synthesize DNA and to secrete IgM and low levels of IgG. B cells activated by anti-Ig antibodies apparently only become responsive to the factor once they have reached late G1 stage. All bioactivities of interleukin 4 are associated with a protein of Mr 44,000 (by NaDodSO4/PAGE). Therefore these results demonstrate that this lymphokine alone is sufficient to induce clonal expansion and maturation of activated B cells.
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PMID:Interleukin 4 (B-cell growth factor II/eosinophil differentiation factor) is a mitogen and differentiation factor for preactivated murine B lymphocytes. 348 87

A rat monoclonal antibody (NIM-R3) was found to be reactive with activated mouse B cells but neither activated T cells nor small resting lymphocytes, T or B. The antibody stains antibody-forming cell precursors within 48 hr of primary or secondary immunization in vivo, but not at longer times (greater than 14 days) immunization. When added to cultures of spleen cells responding in vitro to dinitrophenylated bovine, IgG, the number of antibody-forming cells was increased. NIM-R3 also maintained the proliferation of purified B blasts in the absence of lipopolysaccharide, but did not activate small resting B cells in the presence of anti-Ig. NIM-R3 could replace B-cell growth factor (BCGF II) in cultures of the murine B-cell lymphoma BCL1 inducing proliferation but not differentiation. Finally, competition was demonstrated for binding sites on BCL1 cells between BCGF II and NIM-R3, but not between NIM-R3 and T-cell replacing factor (B15-TRF). We suggest that NIM-R3 may represent a novel specificity and may be directed against the cell surface receptor for BCGF II, and in turn this receptor may be independent of the B15-TRF and BSF1 receptors.
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PMID:Monoclonal antibody NIM-R3 substitutes for B-cell growth factor. 348 71

Prevention of high frequency spontaneous T cell lymphoma development in AKR mice by mAb 18-5 treatment was shown to involve inhibition of the recombinant Class I MCF virus formation and elimination of the early occurring potential lymphoma cells (PLCs). A low B cell lymphoma incidence (16% at a mean latency of 540 days) and a low level of PLCs (yielding 12% B cell lymphoma development following lymphoid cell transfer) was observed in mAb 18-5 treated mice (in contrast to a high PLC level in thymectomized AKR mice that could be experimentally triggered to progress to overt CD5+ B cell lymphomas). Administration of anti CD8 mAb or IL-4 to 12-month-old mAb 18-5 pre-treated mice only slightly increased B cell lymphoma incidence (up to 30-40%). Exposure to split-dose irradiation resulted in 26% B cell lymphomas at a 250 day mean latency. The phenotypes of the B lymphomas developing in mAb 18-5 treated mice were: B220+ (14.8+, 6B2+), 6C3+, Mac2+, CD5-. Most lymphomas expressed l-a and surface IgM, pointing to their mature B cell characteristics. Moreover, in some of the lymphomas, high levels of IgM production and secretion were determined. A comparison of the morphological characteristics (based on light and ultrastructure microscopy) of CD5+ and CD5- B cell lymphomas developing in AKR mice indicated marked differences. Analysis of the IgH locus of representative CD5- B lymphomas showed an identical pattern of IgH rearrangement in some tumors (similar to previous findings among CD5+ lymphomas). The virological analysis of the CD5- B cell lymphomas (similar to those observed in the CD5+ B cell lymphomas of AKR origin) showed that their development did not require formation of the pathogenic MCF recombinant viruses. The differences observed between the CD5+ and CD5- B cell lymphomas developing in AKR mice (following prevention of spontaneous T cell lymphomagenesis) may be due to their origin of different B cell precursors or from B cells at different levels of differentiation.
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PMID:The effects of passive anti-viral immunotherapy in AKR mice: II. Susceptibility to B cell lymphomagenesis. 747 87

The high incidence of spontaneous T cell lymphomas in AKR mice (affected by sustained viremia) can be greatly reduced by experimental manipulations including thymus removal at young age or by genetic manipulation changing the Fv-1 allele that controls replication and spread of viruses (establishing the congenic AKR.Fv-1b mice). Although T cell lymphomagenesis is prevented, all these mice were shown to carry endogenous ecotropic provirus-induced potential lymphoma cells (PLCs) in a dormant state. The termination of the dormant state, leading to a high incidence of CD5+ IgM+ B cell lymphomas, was triggered by interference with T cell functions (optimal effect observed following in vivo administration of anti-CD8 moAb), administration of T cell growth factors or by injecting the MCF-247 recombinant virus isolate (from AKR origin) that affects T cell functions. The assumption that the PLC dormant state is maintained through specific immunological mechanisms (involving T cells or antibodies recognizing PLCs) could not be substantiated experimentally. The results of the present studies suggest that T cells provide immunoregulatory signals or factors that contribute to the maintenance of the B cell lymphoma arrest and/or proliferation. Analysis of cytokine levels produced by splenocytes taken from mice during PLC dormancy or its breakdown indicated reduced levels of IL-2 and IL-4 and marked elevation of IL-1 and IL-6 associated with the termination of the dormant state. The effect of IL-1 and IL-6 on terminating the dormant state was demonstrated by injecting these cytokines into PLC carriers, thymectomized 12-month-old AKR mice, yielding 80-85% CD5+ IgM+ B cell lymphomas. The role of IL-6 on B cell lymphoma proliferation was also indicated in MCF-247 mediated termination of dormancy, by inhibiting significantly its effect via in vivo administration of anti IL-6 moAbs.
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PMID:Role of cytokines in termination of the B cell lymphoma dormant state in AKR mice. 759 76

We have examined the antitumor activity of murine interleukin 4 (IL-4) on development of a human B-cell lymphoma (Daudi) in severe combined immunodeficient (SCID) mice. The progression of Daudi cells in SCID mice was followed by histological staining and by flow cytometric analysis of CD20+ cells in spleen, liver, bone marrow, and kidneys. By day 35, CD20+ Daudi cells populate the majority of space in the bone marrow and kidney in vehicle-treated mice. Mice receiving i.p. injections of IL-4, commencing 7 or 14 days after tumor inoculation, exhibit a reduction in tumor burden as well as a decrease in CD20+ cells in both compartments. The antitumor activity of IL-4 does not appear to be due to an antiproliferative effect, since the cytokine does not alter the growth of Daudi cells in vitro, nor does it correlate with any marked cellular infiltrate in tumor-bearing tissues. In 51Cr-release assays, we observed that splenocytes from IL-4-treated mice were capable of lysing YAC-1 but not Daudi cell targets. Our findings demonstrate that: (a) systemic administration of IL-4 retards dissemination of a human B-cell lymphoma in SCID mice; and (b) antitumor activity elicited by IL-4 may not involve a direct effect on proliferation of Daudi cells or on the induction of cytolytic activity.
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PMID:Interleukin 4 retards dissemination of a human B-cell lymphoma in severe combined immunodeficient mice. 764 Nov 77

JD118 is a murine immunoglobulin M monoclonal antibody (mAb) under study as a therapeutic agent that is capable of potent human complement-mediated cytotoxicity (CMC) against B-cell lymphoma and leukemia targets. The JD118 antigen target was upregulated on fresh human B cells and B-cell neoplasms after brief in vitro incubation in media containing calf serum. To determine if cytokines could also lead to upregulation of JD118 antigen, alpha-interferon (alpha-IFN), gamma-interferon (gamma-IFN), interleukin 2 (IL-2), or IL-4 were added to fresh neoplastic B cells in serum-free media and changes in JD118 antigen expression were evaluated by flow cytometry (FCM). IL-4 was found to be the predominant cytokine responsible for inducing upregulation of the JD118 antigen. Marked JD118 upregulation by IL-4 was seen in 14 out of 14 chronic lymphocytic leukemia (CLL) samples tested, with 50 to 750-fold increases in four samples, 11 to 49-fold increases in four samples, and up to 10-fold increase in six samples. One B-cell lymphoma specimen was upregulated 18-fold, but no up-regulation was demonstrated in one hairy cell leukemia and two acute myelogenous leukemia specimens tested. The specificity of the IL-4 up-regulation was demonstrated by the elimination of its activity by blocking with a neutralizing anti-IL-4 mAb. IL-4 upregulation allows JD118 mAb CMC against otherwise antigen-negative targets and argues for phase I trials using a combination of IL-4 cytokine and mAb for B-cell neoplasms.
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PMID:Interleukin-4 priming enhances a target for human complement-mediated cytotoxicity of CLL. 768 3

Cytokines play important roles in the pathogenesis of lymphomas via an autocrine or a paracrine mechanism, or both. The characteristic clinical and histopathological features of malignant lymphomas may be due in part to elevated serum or tissue levels of cytokines. Determination of the effects of cytokines on the growth or differentiation of lymphoma cells is often complicated by the fact that more than one cytokine is responsible, and by the failure of anti-cytokine antibodies or antisense oligonucleotides to block the proliferation in vitro of lymphoma cells. However, it appears that IL-6 and/or IL-9 may play a prominent role in the tumor cell proliferation of Hodgkin's disease (HD), anaplastic large-cell lymphoma, or immunoblastic lymphoma. IL-6 may also be responsible for the plasmacytoid differentiation of lymphoma cells in polymorphic immunocytoma. The histopathological changes as a result of paracrine effects are most noticeable in HD. The malignant (H-RS) cells of HD have been shown to express IL-1, IL-5, IL-6, IL-9, TNF-alpha, M-CSF, TGF-beta, and CD80, and, less frequently, IL-4 and G-CSF. These cytokines may be responsible for the increased cellular reaction and fibrosis observed in tissues involved by HD and for the immunosuppression found in patients with HD. In contrast to H-RS cells, most non-HD lymphoma cells do not produce cytokines in excess amounts and reveal only a minimal cellular reaction. Exceptions include T-cell-rich B-cell lymphoma, angiocentric T-cell lymphoma, and angio-immunoblastic lymphadenopathy (AILD-like T-cell lymphoma. IL-4 is responsible for the T-cell reaction in T-cell-rich B-cell lymphoma, whereas IL-6 accounts for the plasma cell reaction in AILD-type T-cell lymphoma. The authors extensively review the role of cytokines in lymphomas because this may lead to major advances in the understanding of the molecular processes involved in the histopathogenesis of lymphomas.
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PMID:Autocrine and paracrine functions of cytokines in malignant lymphomas. 785 53

Striking antigenic changes were elicited by interleukin 4 (IL-4) in the Farage human B-cell lymphoma line. After 2 days of incubation with IL-4 the expression of CD23, CD54 (ICAM-1), CD58 (LFA-3) was increased while the levels of CD21, CD22, CD38 were diminished. Prolonged incubation of Farage cells with IL-4 for 6-8 days led to increased expression of CD11a (LFA-1) CD39, CD40, and to disappearance of CD21 and CD38. The modulation of antigenic properties of Farage cells was associated with enhancement of their homotypic adhesiveness and the formation of giant clumps of cells. The recovery of Farage cells which had been exposed to IL-4 for six days was not complete and eleven days after withdrawal of the cytokine, these cells still displayed a lower level of CD21 and of CD38 than control cells. Cycling and non-cycling cells did not appear to differ in their antigenic properties, indicating that modification of the antigenic profile did not result from cell selection or cell arrest. These results showed that the pleiotropic effect of IL-4 on various cell surface structures on malignant human B cells proceeds at different rates suggesting that distinct metabolic pathways may regulate their expression.
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PMID:Kinetics of the pleiotropic effect of interleukin 4 on the surface properties of human B-lymphoma cells. 786 83


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