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

Although the susceptibility of resting B lymphocytes to radiation-induced interphase death is well known, the mechanism by which this occurs is not understood. In this report, we use three measures of plasma membrane integrity (increase in cell volume, uptake of trypan blue, and release of 51Cr) to assess the effect of radiation on the resting B cell plasma membrane. The delivery of 500 to 1000 rad caused the majority of resting B cells to enlarge slightly, whereas 3000 rad caused virtually all of the cells to approximately double in size within 3 to 4 hr. Measurement of the release of 51Cr from resting B cells revealed a similar relationship between the dose of radiation and the loss of radioactive label. Trypan blue exclusion was also found to diminish as a function of radiation dose. An analysis of a variety of lymphoid cells suggested that sensitivity to the membrane damaging effects of gamma radiation was in the order of resting B cells greater than resting T cells greater than a long-term L3T4+ T cell clone greater than a B cell lymphoma. LPS-induced B cell blasts treated with 3000 rad were equivalent to 1000 rad-treated resting B cells. The effects of the gamma radiation could be ameliorated by excluding oxygen (a diradical molecule that can potentially enhance the generation and propagation of highly reactive free radicals) at the time of irradiation, or by adding the free radical scavenging agent cysteamine. These data are compatible with the hypothesis that gamma radiation results in damage to the plasma membrane of resting lymphocytes via the generation of highly reactive free radical species. This damage is reflected in a rapid increase in plasma membrane permeability and swelling of the cells, and may play a major role in causing interphase death.
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PMID:Effect of gamma radiation on resting B lymphocytes. I. Oxygen-dependent damage to the plasma membrane results in increased permeability and cell enlargement. 308 37

To study T cell regulation of B cell isotype differentiation, we determined the capacity of clonal T cell populations (hybridomas derived by fusing BW5147 with Con A-activated Peyer's patch (PP) and spleen T cells) to induce "downstream" isotype expression by the pre-B cell lymphoma 70Z/3. In initial studies, we found that 70Z/3 B cells cultured in the presence of LPS (1 microgram/ml) expressed membrane IgM (mIgM) but not membrane IgG (mIgG). In contrast, 70Z/3 B cells cultured with HAJ-3 T cells, a PP-derived T cell hybridoma (as well as other similarly derived PP and spleen hybridomas), or with HAJ-3 T cells plus LPS do express mIgG. Such expression occurred in spite of mitomycin C-induced blockage of cell proliferation, and is observed in 70Z/3 B cell subclones cultured with HAJ-3 T cells. For these reasons, it is not due to selective expansion of a small pre-switched mIgG-bearing 70Z/3 B cell subpopulation. In other studies it was shown that 70Z/3 B cells expressing mIgG after induction by HAJ-3 T cells continue to express mIgM and do not secrete IgG. Finally, exposure of 70Z/3 B cells to the macrophage factor IL 1 and the T cell factors IL 2, BSF-pl, and BCGF-II present in EL-4 cell supernatants did not result in mIgG expression. On the basis of these studies, we conclude that a clonal B cell population expressing mIgM can be induced by T cells to co-express mIgG. Because the B cells do not express mIgG unless exposed to T cells, this represents a T cell-induced isotype switch.
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PMID:T cell-induced expression of membrane IgG by 70Z/3 B cells. 308 58

The murine B cell lymphoma, 70Z/3, serves as a model for the L chain activation seen when normal B cells develop from pre-B into B cells. 70Z/3 cells can be induced to activate transcription of their endogenous kappa L chain by exposure to exogenous factors in vitro, such as LPS and IFN-gamma. In order to study the interaction of transacting factors with sequences of the kappa gene responsible for their activation, altered kappa genes could be introduced into 70Z/3 cells and their induction patterns studied. As a preliminary step to such studies, we show that wild-type kappa genes stably integrated into 70Z/3 cells can be expressed normally and that their pattern of induction by LPS and IFN-gamma is indistinguishable from wild-type 70Z/3 cells. By using electroporation, gamma genes were co-transfected with either the neo or gpt selectable genes. In all cases, the expression of the kappa genes was autonomous, reflecting neither regulation by the selected markers nor by flanking chromosome sequences. A noninducible variant of 70Z/3, NN12, also increased mRNA levels from transfected kappa genes in response to LPS and IFN-gamma, suggesting that its defect is in its endogenous kappa gene. These results demonstrated the usefulness of this approach for distinguishing between variants that have structural defects in their endogenous kappa gene from variants that have defects in transacting factors or other steps in the induction pathways.
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PMID:Inducible expression of transfected kappa light chains by lipopolysaccharide and IFN-gamma in the murine B lymphoma, 70Z/3. 312 55

The I.29 B cell lymphoma consists of IgM+ and IgA+ cells which express the same germ-line VH gene. IgA+ cells of the I.29 lymphoma were derived from the IgM+ cells by a typical H chain switch recombination event. The IgM+ cells can be induced with LPS to undergo H chain switching in culture. It has been proposed that the somatic hypermutation process is activated during H chain switch, since V genes expressed in IgG+ and IgA+ cells have more frequently undergone mutation than those expressed in IgM+ cells. We have investigated this question by sequencing VH genes expressed before and after H chain switch in the I.29 lymphoma. We have also sequenced the germ-line VH gene corresponding to the gene expressed by I.29 cells to determine whether the VH gene expressed in the IgM+ cells had already undergone somatic mutation. Our results indicate that somatic mutation was not activated in the precursor cell for the I.29 lymphoma, nor during isotype switch in I.29 cells. It is possible that cells of the I.29 lymphoma, or their precursor, have not received the signal which induces somatic mutation, or that I.29 cells belong to a subset of B cells that cannot be induced to undergo any (or much) somatic mutation.
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PMID:I.29 lymphoma cells express a nonmutated VH gene before and after H chain switch. 312 34

We have selected and cloned variant cells from the murine B cell lymphoma, CH12, that produce a variety of other Ig isotypes in addition to or in place of the original IgM and IgD. Variants were selected by flow cytometry and automated cloning and isotype production was analyzed by membrane immunofluorescence and ELISA of culture fluids. Variants have been isolated that produce the single isotypes IgA, IgG2b, and IgG3, as well as variants that produce more than one isotype simultaneously, i.e., IgM, IgD, and IgA; IgG2b and IgA; IgG3 and IgA. All isotypes have been seen as cell surface proteins and all except IgD have been found in culture supernatants. All isotypes display the same idiotype and Ag-binding specificity for phosphatidyl choline as the original IgM and all are translated from the same VDJH and VJ kappa gene assemblies. Production of more than one isotype by a variant clone is due to simultaneous production of all the isotypes by each cell within the clone. The finding that the variants producing more than one isotype are all tetraploid suggests the interesting possibility that each isotype is derived from an independently switching chromosome. All isotype variants can be stimulated by LPS to secrete the appropriate Ig isotype at an increased rate similar to the IgM expressing parent. The variants differ in stability; some have remained stable for more than 9 months in culture, whereas other have undergone further isotype switching. The facts that some isotypes have not been seen, that multistep switching has occurred, and that many variants produce IgA in addition to another isotype are discussed in relation to current notions of isotype switching mechanisms.
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PMID:Ig isotype switching in B lymphocytes. Isolation and characterization of clonal variants of the murine Ly-1+ B cell lymphoma, CH12, expressing isotypes other than IgM. 313 32

Vaccination of mice with tumor-derived idiotypic IgM from the B cell lymphoma, BCL1, induces an anti-idiotypic immune response which suppresses tumor development. One of the mechanisms by which tumor cells can escape attack is by failing to express significant levels of idiotypic immunoglobulin at the cell surface, and a stable variant of this phenotype has been isolated. The variant, termed SNAG 1, continues to synthesize idiotypic IgM, which can be detected in the cytoplasm, but it neither secretes nor expresses IgM on the cell surface (less than 10% of the levels of the original BCL tumor), even though the H and L chains show no gross structural changes. The SNAG 1 cells resemble the parent BCL cells in morphology, in expression of MHC class I and II Ag and in bearing FcR. A significant difference between the BCL lymphoma cells and the variant cells is that the latter fail to respond to LPS by either DNA synthesis or secretion of IgM, suggesting that surface Ig might be required for such a response. The variant has a slower rate of division than the parent tumor both in vitro and in vivo, and a rather different organ distribution. Study of such variants might allow analysis of the mechanisms involved in surface Ig expression and its possible role in tumor cell growth and migration.
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PMID:Idiotype vaccination leads to the emergence of a stable surface Ig-negative variant of the mouse lymphoma BCL1, with different growth characteristics. 316 50

T cell-replacing factor (TRF)/IL-5 is a glycosylated polypeptide that acts as a key factor for B cell growth and differentiation. Since IL-5 action is probably mediated by specific cell surface receptor(s), we have characterized the binding of IL-5 to cells using biosynthetically [35S]methionine-labeled IL-5 and 125I-IL-5 that had been prepared using Bolton-Hunter reagent. The radiolabeled IL-5 binds specifically to BCL1-B20 (in vitro line) (a murine chronic B cell leukemic cell line previously shown to differentiate into IgM-secreting cells in response to IL-5) within 10 min at 37 degrees C. There are two classes of binding sites with high affinity (Kd = 66 pM) and low affinity (Kd = 12 nM) for IL-5 and an average number of binding sites for high affinity and for low affinity were 400 and 7,500 per cell, respectively. The specificity of binding of radiolabeled IL-5 has been confirmed by demonstrating that only unlabeled IL-5 and anti-IL-5 mAb but not by IL-1, IL-2, IL-3, IFN-gamma, and GM-CSF inhibit radiolabeled IL-5 binding to BCL1-B20 cells. Treatment of surface-bound radiolabeled IL-5 with bivalent crosslinkers identified a membrane polypeptide of Mr 46,500 to which IL-5 is crosslinked. A variety of cell types have been surveyed for the capacity to bind specifically radiolabeled IL-5 with high affinity. BCL1 cells MOPC104E (murine myeloma cell line) expressed IL-5-R, whereas BAL. 17 and L10 A (B cell lymphoma) did not. T cell line, mastocytoma cell line, or macrophage tumor cell line did not display detectable levels of IL-5-R. were hardly detectable on normal resting B cells but were expressed on LPS-activated B cells, fitting the function of IL-5 that acts on activated B cells for their differentiation into Ig-secreting cells. Intriguingly, early B cell lines (J-87 and T-88) that grow in the presence of IL-5 expressed significant but low numbers of high-affinity binding sites for IL-5. The biological effects of IL-5 were mediated by high-affinity binding sites. The identification and characterization of IL-5-R should provide new insight into the apparent diverse biological activities of IL-5.
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PMID:Receptors for T cell-replacing factor/interleukin 5. Specificity, quantitation, and its implication. 326 7

A series of B cell hybridomas was used as a model system to assess quantitatively the role of Ia molecules in antigen presentation to allo- or soluble antigen-reactive T cell clones. These hybrid cell lines were established by fusion between the HGPRT-BALB/c B cell lymphoma M12.4.1 and LPS-stimulated spleen blasts from B10.BR (H-2k) mice. Quantitative cellular absorption of appropriate anti-Ia monoclonal antibodies and flow cytofluorometric analyses revealed that the B cell hybridomas examined herein expressed constitutively a number of surface I-Ak or I-Ek molecules that varied in an order of magnitude of 1 to 5. Such quantitative differences could be correlated precisely with (a) the capacity of B cell hybridomas to activate T cell clones to proliferate and/or to produce interleukin 2 in response to E beta k allodeterminant or to poly(Glu60Ala30Tyr10) presented in the context of I-Ak restriction element, and (b) the amount of monoclonal anti-I-Ak antibody required to inhibit antigen presentation to T cell clones. The possible implications of these data are discussed in the context of current models of regulation of Ia antigen expression by antigen-presenting cells.
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PMID:Efficiency of antigen presentation to T cell clones by (B cell X B cell lymphoma) hybridomas correlates quantitatively with cell surface ia antigen expression. 633 37

Phenotypic characterization by monoclonal antibodies of spleen cells obtained from three spleens involved by hairy cell leukemia (about 90% of cells with intracytoplasmic tartrate-resistant acid phosphatase) indicated that the hairy cells are OKT-3-, OKM-1+, and OKIa1+. Neoplastic cells obtained from two lymph nodes involved by B-cell lymphoma were found to be OKT-3-, OKM-1-, and OKIa1+. Functional characterization of the hairy cells present in the spleen indicated that they lack NK activity and do not release Interleukin 1. In fact, spleen hairy cells were not lytic against K-562 tumor cells in a short-term 51Cr-release assay and did not release Interleukin 1 in culture supernatants even after LPS stimulation. In normal individuals, both these cell functions are expressed by subpopulations of OKM-1+ cells.
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PMID:Hairy cell leukemia: absence of natural killer activity and of interleukin 1 release in OKM-1+ spleen hairy cells. 660 5

The low affinity receptor for IgE (Fc epsilon RII or CD23), expressed primarily on mouse B cells, is known to be upregulated by interleukin-4 (IL-4) at both the mRNA and protein levels. Fc epsilon RII expression is superinduced when the IL-4 is combined with cell activation. In order to explore the molecular regulation of Fc epsilon RII expression, mouse B cell lines were screened to develop a cell line model. The B cell lymphoma A20.1, was found to behave in a manner similar to mouse B cells in that Fc epsilon RII levels are very low on cells cultured in media alone (< 10(3)/cell), increased by culture in the presence of IL-4, and superinduced by LPS and IL-4 (> 10(5)/cell). The steady state mRNA levels for Fc epsilon RII corresponded to the level of cell surface expression. Transcription assays indicated that the Fc epsilon RII level increases could be explained entirely by increased transcription rates. The A20.1 cell line was subsequently used to analyse the Fc epsilon RII promoter. Nested deletion analysis of the 1.3 kB 5' of the mouse Fc epsilon RII transcription start site, using CAT reporter plasmids transfected into A20.1 cells, identified major elements activating the Fc epsilon RII promoter within 250 bp of the transcription start site. Constructs containing greater than 250 bp of 5' sequence showed significantly reduced CAT activity suggesting negative regulatory regions. Coincident with the restricted tissue expression of murine Fc epsilon RII, the promoter was B cell specific in that little CAT expression was seen in fibroblast, mast cells or T cell lines. Expression was seen, however, in both mouse and human B cell lines. Finally, the promoter was analysed for response to IL-4. Stimulation with IL-4 plus LPS resulted in only a modest increase in CAT activity (approximately 2-fold), in contrast to transcription assays, where increases approximated that seen at the cell surface. Thus, the IL-4 response must also require sequences distal to the regions examined.
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PMID:Molecular mechanisms of murine Fc epsilon RII/CD23 regulation. 793 5


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