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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 murine B cell lymphoma CH12.LX, which bears cell surface IgM specific for the phosphatidyl choline epitope of sheep red blood cells, is capable of spontaneous isotype switching in vitro. Switching to IgG3, IgG1, IgG2b, and IgA has been observed and variants expressing those isotypes have been isolated and cloned. We have developed a procedure for precise numerical evaluation of the frequency of switching to the several isotypes to which CH12.LX can switch. We have used a modified Poisson method which can distinguish between treatments which change isotype switch frequency and those which affect, in an isotype-specific fashion, growth or secretion rates of cells which have already switched. In this report we examine the effect of several cytokines, cholera toxin, hydroxyurea, and antigen on the isotype switch frequency of CH12.LX. The strongest effect observed was that of transforming growth factor-beta, which increases switch frequency 40-fold to an absolute switch frequency of 0.04 switch events (from IgM to IgA expression) per cell division. Interleukin-4 (IL-4) and cholera toxin also increase the switch frequency of CH12.LX while IL-5, IL-6 (with or without antigen), antigen (SRBC) alone, interferon-gamma, or hydroxyurea have no effect. We have shown that none of the cytokines studied change the relative frequency of switching to the available isotypes, only the absolute frequency of switching. We infer from this that the factors tested do not 'instruct' CH12.LX to switch to a particular isotype, but rather they deliver a 'go' signal to cells committed to switching to IgA at high frequency, rarely to IgG3, IgG1, or IgG2b, and never to IgG2a or IgE.
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PMID:Ig isotype switching in B lymphocytes. The effect of T cell-derived interleukins, cytokines, cholera toxin, and antigen on isotype switch frequency of a cloned B cell lymphoma. 204 38

We have utilized cultured Langerhans cells to activate and expand hapten- and protein-specific T-helper cells from nonsensitized mice. The generation of these lines was strongly dependent on eliminating all autologously reacting cells from the responder T-cell population. Primary in vitro sensitization was not uniquely induced with cultured Langerhans cells as splenic dendritic cells could subserve the same function. Despite its ability to induce strong allogeneic T-cell responses as well as hapten-specific secondary responses, M12c cells, a class II-bearing B-cell lymphoma line, could not activate hapten-specific T-helper cells in vitro. After primary or secondary in vitro stimulation, the T-helper cells which are generated secrete IL-2 and are able to adoptively transfer hapten-specific contact sensitivity, thus stimulating Type-1 T-helper cells. The T-helper cell lines which were generated after repeated cycles of stimulation stimulated type-2 T-helper cells in that they produced IL-4 and depended on this cytokine for autocrine growth. As well, when cultured with syngeneic, hapten-modified, small resting B cells, these T-helper cells caused specific IgE production. Thus, the studies reported herein demonstrate that it is possible to activate and expand T-helper cells with desired specificity from nonsensitized animals in vitro. Previous studies have demonstrated that expansion and adoptive transfer of effector T cells with specificity for tumor-associated antigens may be useful in the control of certain tumors; T-helper cells generated by in vitro sensitization should also be useful in adoptive immunotherapy.
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PMID:Generation and characterization of T-helper cells by primary in vitro sensitization using Langerhans cells. 214 19

The murine B cell lymphoma I.29 contains cells expressing surface IgM or IgA with identical heavy chain variable regions (9, 25, and D. Klein and J. Stavnezer, unpublished data). Purified IgM+ cells from the lymphoma have been adapted to culture and induced to switch to IgA, IgE, or IgG2 by treatment with lipopolysaccharide (LPS) or by treatment with a monoclonal anti-I.29 antiidiotype plus LPS. Clones of IgM+ cells have been obtained and induced to switch. Under optimal conditions, 30% of the cells in the culture expressed IgA 8 d after the inducers were added, and by 15 d 90% of the cells were IgA+. In actively switching cultures, up to 50% of the cells whose cytoplasm stained positively with anti-IgA stained simultaneously with anti-IgM, which indicates that the appearance of IgA+ cells in the cultures was due to isotype switching and not to clonal outgrowth. Examination by Southern blotting experiments of the Ig heavy chain genes in I.29 cells before and after switching revealed that isotype switching was accompanied by DNA recombinations that occurred within or immediately 5' to the tandemly repeated switch sequences. Within 3 d after the addition of inducers of switching, the nonexpressed chromosome underwent a variety of deletions or expansions within the S mu region, and a portion of the S alpha regions had undergone a 0.9-kb deletion. In cultures that contained at least 12% IgA+ cells, rearranged, expressed alpha genes, produced by recombination between the S mu region within the expressed mu gene and the S alpha region, were detected.
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PMID:Induction of immunoglobulin isotype switching in cultured I.29 B lymphoma cells. Characterization of the accompanying rearrangements of heavy chain genes. 257 86

IgM+ cells cultured from the I.29 B cell lymphoma can be induced with lipopolysaccharide (LPS) or, to a greater extent, with LPS plus anti-idiotype antibody to switch to IgG2a, IgE or IgA expression. The isotype switch is accompanied by rearrangement of immunoglobulin (Ig) heavy (H) chain genes. Here we demonstrate that the commitment of the I.29 IgM+ cells to switch to IgA appears to be manifested by hypomethylation of the alpha constant region genes in IgM+ cells, and by the presence of small amounts of RNAs transcribed from non-rearranged alpha gene(s) in IgM+ cells. The commitment to switch to IgE or IgG2a is also in accord with the presence of small amounts of RNA transcripts from the non-rearranged epsilon and gamma 2a genes, although the hypomethylation of the epsilon and gamma 2a genes is not as dramatic as that of the alpha genes. These results suggest that I.29 cells switch specifically to IgA, IgE or IgG2a due to the activation of the corresponding H chain constant region genes in IgM+ cells prior to the actual switch recombination event.
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PMID:Specificity of immunoglobulin heavy chain switch correlates with activity of germline heavy chain genes prior to switching. 300 21

Cells from the monoclonal B cell lymphoma I.29 expressing surface IgM (mu +) are capable of differentiating in vitro to IgM secretion and of switching to IgA or IgE production in response to lipopolysaccharide (LPS) stimulation. To determine whether a single mu + B cell is capable of undertaking both differentiative pathways (isotype switch and plasma cell differentiation) I.29 mu + cells were cloned by limiting dilution and a panel of clones were analyzed by immunofluorescence, endogenous labeling and Northern blotting. While 100% of the clones could differentiate toward IgM secretion, only a proportion of them (greater than 70%) also switched to IgA and/or IgE production. Certain clones switched preferentially to a specific isotype. Taken together with the observation that C gamma genes were never the target of switching in our experiments, these data suggest that individual mu + clones from the I.29 lymphoma are "precommitted" as for their switching potentials. The subclones that showed a high frequency of switching to IgA transcribed the germ line C alpha gene(s), suggesting a role for chromatin structure in determining the isotype switch specificity. Switch variant clones expressing either IgA or IgE on the cell surface were isolated and found capable of further differentiating toward Ig secretion in response to LPS. On the contrary, we could not induce switch to IgA in IgE-producing cells. Unlike mu + and alpha + cells, all the switch variant clones expressing IgE tested by endogenous labeling constitutively secreted large amounts of IgE in the supernatants even in the absence of LPS stimulation.
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PMID:Differentiation in the murine B cell lymphoma I.29: individual mu + clones may be induced by lipopolysaccharide to both IgM secretion and isotype switching. 310 70

A switch variant of the I.29 murine B-cell lymphoma expressing membrane IgE and inducible by lipopolysaccharide (LPS) to increase the rate of IgE secretion was characterized. The cells (I.29 epsilon +2) express membrane-bound IgE, and also secrete considerable amounts of IgE when grown in regular culture medium. Membrane and secreted IgE contain structurally different heavy chains. The former is constituted by a 93-kd molecule (epsilon m), while secretory chains (epsilon s) have an apparent mol. wt of 86,000. Both epsilon m and epsilon s are heavily glycosylated: in the presence of tunicamycin their apparent mol. wt is reduced by approx. 35% (61 kd for epsilon m and 56 kd for epsilon s). Glycosylation is necessary for membrane expression and for secretion of IgE molecules. Stimulation with LPS leads to the disappearance of IgE molecules from the cell surface (determined by radioiodination) although epsilon m-chains are still synthesized, suggesting a defective transport of membrane IgE in LPS-treated cells. The epsilon m:epsilon s ratio decreases upon LPS stimulation. A similar change can be observed in the messenger RNAs specific for epsilon m and epsilon s, possibly suggesting a major pretranslational control for epsilon m and epsilon s biosynthesis.
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PMID:Biosynthesis of membrane and secreted epsilon-chains during lipopolysaccharide-induced differentiation of an IgE+ murine B-lymphoma. 393 17

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

Plasma levels of the soluble fragments of Fc epsilon RII/CD23 (sCD23/IgE-binding factor) were measured to assess the level of activation of B lymphocytes associated with Epstein-Barr virus infection in 28 patients who received living-related liver transplantation and were treated with FK506 and steroids. In 6 patients with symptoms of EBV infection (EBV-related disorders), the plasma concentration of sCD23 increased to more than 9.8 ng/ml at the onset of symptoms. In a patient with B cell lymphoma, the plasma levels of sCD23 increased significantly when peripheral lymphadenopathy was noticed, and remained more than 10 ng/ml during the terminal period. In 4 of 6 patients, the increase of plasma levels of sCD23 preceded the increase of anti-EBV capsid antigen IgM. In the other 2 of 6 patients, there was no significant increase of the antibody, despite the integration of EBV DNA in the mononuclear cells in their ascites. The plasma levels of sCD23 of the patients without symptoms of EBV infection did not exceed 7.5 ng/ml. In contrast, the proportion of CD20+/CD23+ B lymphocytes in peripheral blood mononuclear cells was not significantly different in the patients with EBV-related disorders and those with latent asymptomatic EBV infection. Therefore, the plasma level of sCD23 is a sensitive and useful marker of EBV-related polyclonal and/or monoclonal B cell proliferation in transplanted patients with immunosuppression.
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PMID:Soluble CD23 as a sensitive marker for Epstein-Barr virus-related disorders after liver transplantation. 824 9

Omenn syndrome is a variant of SCID, inherited as an autosomal recessive disorder, and characterized by severe eczematoid dermatitis, eosinophilia, elevated serum IgE and a distinctive histology in enlarged lymph nodes. The etiology of Omenn syndrome is unknown, however, unlike other forms of SCID; patients with Omenn syndrome have activated T lymphocytes in their circulation capable of non-MHC restricted cytotoxic function. Recently, it has been observed that the use of immunosuppressive therapy, particularly cyclosporine, can modify the clinical manifestations of the disorder. Prior to the use of bone marrow transplantation this disease was universally fatal. Death typically occurred in infancy as the result of opportunistic infections and/or malignancies, most notably lymphomas. While bone marrow transplantation has become quite successful for many phenotypes of SCID, even with the use of alternative donors other than histocompatible siblings, in Omenn syndrome it remains a challenge. In our experience, patients with Omenn syndrome exhibit a higher incidence of Gram negative sepsis, before and during transplantation, and carry a significant risk of post-transplant rejection when compared with patients with other phenotypes of SCID. We report the results of six patients treated with bone marrow transplantation from alternative donors, three had unrelated donors (URD) and three had haplo-identical parental donors. Five of the six patients achieved complete and/or durable donor cell engraftment and only one patient experienced acute GVHD. Three patients died of transplant-related complications (infection or EBV-associated B cell lymphoma) between day +22 and day +95 post-transplant. Three patients survived more than 1 year post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mismatched bone marrow transplantation for Omenn syndrome: a variant of severe combined immunodeficiency. 853 10

Investigations of VH gene mutational patterns in B-cell tumors are often performed at an arbitrary time point of disease. To assess the effects of disease progression, tumor-derived VH genes have been monitored from presentation through treatment and relapse in one patient with follicle center lymphoma (FCL), and two patients with primary diffuse large B-cell lymphoma (DLCL). The patient with FCL and one patient with DLCL both achieved clinical remission, although this was only partial in the FCL. However, both subsequently relapsed, and the second patient with DLCL was refractory to radiotherapy and chemotherapy. In each case, the tumor-derived VH sequence was identified, and the CDR3 "clonal signature" was used to track tumor cell sequences in subsequent biopsies. All cases showed somatic mutations, with intraclonal heterogeneity evident at presentation, and some sequences were aberrant. The VH sequences of the DLCL which responded to treatment became homogeneous at relapse. The sequences of both the FCL and the refractory DLCL remained heterogeneous. In all cases, transcripts of multiple Ig isotypes could be identified, and there was immunophenotypic evidence for expression of several Ig isotypes. The case of refractory DLCL had identifiable transcripts from IgM, IgD, IgA, IgG, and IgE, but appeared to lose the ability to produce alternative isotype transcripts and protein at the late stage of disease. These cases indicate that VH gene analysis can be used to probe tumor cell behavior in cases of lymphoma and that perturbations caused by therapy and disease progression can occur.
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PMID:Analysis of VH genes in follicular and diffuse lymphoma shows ongoing somatic mutation and multiple isotype transcripts in early disease with changes during disease progression. 959 78


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