PubMed Health⌕ Search

Biomedical subjects

I Ernberg

Publications and source records attributed to I Ernberg.

At least 109 records · Page 6Linked to original sources

Epstein-Barr virus transformation of human pre-B cells.

In vitro infection of human B lymphocytes with Epstein-Barr virus (EBV) results in establishment of B lymphoblastoid cell lines that reflect normal B cell phenotypes. In this study we have investigated whether immature B cells from fetal bone marrow and liver can serve as targets for EBV. The fetal bone marrow cells were readily transformed by EBV. Among the resulting cell lines, five were surface Ig (sIg)-negative. Three B cell-associated antigens defined by monoclonal antibodies were expressed to the same extent on the fetal cell lines, whether they belonged to the sIg- or sIg+ group. The various differentiation stages that these cell lines may represent are discussed.

Antibody-Producing Cells↗

Relationship between the amounts of EBV-DNA and EBNA per cell, clonability and tumorigenicity in two ebv-negative lymphoma lines and their EBV-converted sublines.

The effect of EBV-conversion of two EBV-negative lymphoma lines (Ramos and BJAB) on agarose clonability and tumorigenicity in nude mice was explored. The cloning frequency was increased in all 9 sublines investigated, between 1.1 and 4.9 times compared to the original "parental" lines. Tumorigenicity was increased in one out of 2 BJAB-derived, EBV-positive lines and in 3 of 6 Ramos-derived lines, while it was decreased in 3 others. A strong positive correlation between the number of genomes/cell and the amount of EBNA/cell was detected, and in 7 of 9 converted lines the cloning frequency also correlated to the number of EBV genomes. On the other hand, no relation was established between the number of EBV-genomes/cell, the amount of EBNA/cell and tumorigenicity.

Animals↗

Epstein-Barr virus (EBV)-induced lymphoproliferative disease in cotton-topped marmosets.

Six cotton-topped marmoset monkeys (Sangiunus oedipus) were inoculated with 10(5) transforming units of B95-8 virus, and two of them developed fatal lymphoproliferative disease. The EBV-carrying tumor cells from these marmosets had the following characteristics: (1) they were polyclonal by surface immunoglobulin and immunoglobulin production in vitro; (2) they had no specific chromosome abnormalities, and (3) they failed to form colonies in large percentages in agarose. It is proposed that a spectrum of phenotypes of EBV-induced lymphoproliferative diseases in the cotton-topped marmosets may be identified and are more akin to fatal infectious mononucleosis or X-linked lymphoproliferative syndrome than to Burkitt's lymphoma.

Animals↗

Can Epstein-Barr virus infect and transform all the B-lymphocytes of human cord blood?

Quantitative aspects of Epstein-Barr virus infection and transformation of human neonatal B-lymphocytes have been investigated. 72 to 90% B-cells were obtained with enrichment. Of the B-cells, 19 to 97% showed nuclear antigen (EBNA) 2 days after infection. A difference between different B-cell donors in susceptibility to infection was noted. Analysis of the virus dose-response curves obtained with twofold virus dilutions showed that one virus particle is sufficient to induce EBNA in a cell. Of the infected cells, 50 to 95% multiplied in microtitre wells containing a human fibroblast feeder layer, while only a small proportion established growing colonies in soft agarose, that could be picked up and subcultured.

Animals↗

Human T cell growth factor (TCGF) produced by repeated stimulation of non-adherent human lymphocytes.

T cell growth factor (TCGF) has become a valuable means of maintaining T lymphocytes in long-term culture and of studying T cell function. Numerous problems have been met in the production of TCGF of consistently good quality and in the maintenance of human T cell lines over long periods. We have investigated optimal conditions for TCGF production, and simplified assay systems for TCGF activity. The best TCGF production was obtained by short-term treatment with high concentrations of phytohemagglutinin (PHA). The TCGF producing lymphocytes could be re-used for TCGF production up to 1 month after the first treatment course. Human cultured T cell lines, fresh lymphocytes, short-term PHA stimulated lymphocytes and cultured marmoset T lymphocyte lines were all used for assay of TCGF. We recommend PHA stimulation of human lymphocytes for this assay on a routine basis, comparing results with a standard TCGF batch and calculating a growth index. Adherent cells impair TCGF production. Optimal TCGF production was seen when lymphocyte preparations without adherent cells from different donors were used.

Animals↗

Human lymphoma-lymphoma hybrids and lymphoma-leukemia hybrids. II. Epstein-Barr virus induction patterns.

In addition to the spontaneous expression of markers of the early and late phases of the viral cycle [Epstein-Barr virus (EBV), early viral cycle antigens (EA), and viral capsid antigen (VCA)] by a Panel of hybrid cell lines derived by fusion of human hematopoietic cell lines, the induction of these markers by three chemical inducers [5-iodo-2'-deoxyuridine, the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA), and sodium butyrate] were analyzed. A variant of the prototype producer of lytic EBV, P3HR-1 (PICAT) was observed to show consistent low spontaneous and induced production of EA and VCA as compared to the P3HR-1 line from which it was derived. An "autohybrid" (PICATPO-1) between these two lines showed a low production of VCA. Hybrids between Raji and P3HR-1 sublines (RUD-PICAT-1 and RUDPUT-2) showed reduced expression of EBV antigens. Both hybrids were capable of VCA expression, in contrast to the Raji parent that expressed EA but not VCA. A new Raji-Daudi hybrid (DITRUD-1) expressed spontaneous and induced EA and VCA at levels intermediate between its two parents. A different type of hybrid was derived from a Daudi subline and the K562 leukemia cell line (DUTKO-1) and was found to be capable of spontaneous as well as induced EA and VCA expression. Both DUTKO-1 and DITRUD-1 were similar to Daudi in their induction profile in respect to a very low response to TPA.

Animals↗

Characteristics of Epstein-Barr virus activation of human B lymphocytes.

Epstein-Barr virus (EBV) will infect at least every third cell if exposed in vitro to an extensively purified B cell population from human peripheral blood. About 10% of such infected cells will be driven into immunoglobulin synthesis and secretion, as judged by the indirect protein A plaque assay. The appearance of EB nuclear antigen, de novo DNA synthesis, and immunoglobulin secretion are linked phenomena accompanying infection as judged by viral dilution experiments, which yield kinetics of a one-hit order. Induction of immunoglobulin secretion in B cells by EBV requires de novo synthesis of DNA, and consequently, nontransforming EBV (P3HR1) will not induce immunoglobulin secretion and will also specifically block such induction from subsequently added EBV. The termination of immunoglobulin induction by EBV in short-term cultures appears to be T cell dependent.

Antibody Formation↗

Use of cryopreserved lymphocytes for the indirect leukocyte migration inhibition assay.

Production of leukocyte migration inhibitory factor (LIF) by fresh and cryopreserved lymphocytes from the same donors was detected by indirect leukocyte migration inhibition (LMI) assay. The same results were obtained when fresh and frozen lymphocytes were tested in parallel. This indicates that cryopreservation does not impair the ability of lymphocytes to produce LIF.

Freezing↗

Induction of Epstein-Barr virus early antigen, virus capsid antigen and virus DNA synthesis by mitomycin C.

The effect of mitomycin C was tested on Epstein-Barr virus (EBV) antigen and virus DNA synthesis in producer and non-producer cell lines. We found that producer, but not non-producer cell lines, are inducible for early antigen and virus capsid antigen synthesis. Although host DNA synthesis is effectively inhibited by over 99% in the presence of mitomycin C, virus DNA synthesis in the producer lines is unaffected and induced in parallel with the virus antigens.

Antigens, Viral↗

An EBV-associated, Swedish case of Burkitt-type malignant lymphoma.

Morphological, serological, DNA-homology and immunofluorescence studies of a rapidly fatal malignant lymphoma in a 25-year-old Sweden male revealed most of the characteristics of an EBV-associated Burkitt lymphoma. The various findings are discussed in relation to previously reported observations on endemic (African) and non-endemic Burkitt lymphomas.

Adult↗

Cell surface glycoprotein patterns of two EBV-negative lines and their EBV converted sublines.

Cell surface galactosyl-glycoprotein patterns were compared between Ramos and BJAB, two Epstein-Barr virus (EBV)-negative Burkitt lymphoma lines, and their acutely EBV-superinfected and stably EBV-converted derivatives. A major difference between Ramos and its EBV-infected variants was the appearance of a 69,000 mol. wt. galactosyl-glycoprotein (GP69) in the latter. The same phenomenon was found in BJAB along with the additional appearance of a 71,000 mol. wt. galactosyl-glycoprotein (GP71) in the EBV-infected cells. GP71 was present in Ramos and in its EBV-converted derivatives.

Burkitt Lymphoma↗

Cellular immune defects to Epstein-Barr virus-determined antigens in young males.

Three males with the X-linked lymphoproliferative syndrome (XLP) with hypo- or agammaglobulinemia following Epstein-Barr virus (EBV) infection and two males with the chronic mononucleosis syndrome were investigated for immune responses to EBV-determined antigens. Males with XLP showed profound cellular immune defects. Markedly diminished responses of natural killer cell and interferon-activated killer cell activities and impaired leukocyte migration inhibition responses to phytohemagglutinin were determined in patients with XLP. The two patients with chronic mononucleosis showed less severe defects. All patients showed partial or complete impairment of their EBV-specific immune responses as measured by leukocyte migration inhibition. EBV-specific antibodies were markedly diminished against EBV-associated nuclear antigen, early antigen, and viral capsid antigen in males with XLP. In contrast, patients with chronic mononucleosis had elevated antibodies to most EBV-specific antigens. Individuals with life-threatening EBV-induced lymphoproliferative disorders may exhibit multiple defective immune mechanisms against the virus.

Adolescent↗

Proliferation inhibitory effect of human alpha interferon on primary explants of Burkitt lymphoma: inverse relationship to patient survival.

Eleven biopsies from 9 patients with Burkitt's lymphoma were tested for their sensitivity to the cell multiplication inhibitory activity of interferon. Three were resistant to interferon while 8 were sensitive to various degrees. Different biopsies from the same patient did not differ in interferon sensitivity. These results indicate that Burkitt's lymphoma cells might be resistant to interferon already in vivo as previously shown for some derived cell lines tested in vitro. The results imply an inverse relationship between patient survival and interferon sensitivity of the tumor cells.

Burkitt Lymphoma↗

T-cell response to B-cells and Epstein-Barr virus antigens in infectious mononucleosis.

After Epstein-Barr virus (EBV) infection in vivo, B-cells with latent virus infection persist indefinitely through life. These cells grow in vitro on explanation and can be established as immortal B-cell lines. To reconcile the unlimited growth potential in vitro with the maintenance of a low proportion of B-cells infected by EBV in vivo, a strict in vivo control mechanism has to be postulated. Certain aspects of this control are apparent when the primary infection is followed by infectious mononucleosis. This is characterized by lymphocytosis and the presence of activated T-cells. The T-cell proliferation is probably the manifestation of the immune response against EBV antigens. However, the reaction of T-cells upon encounter of B-blasts is also likely to contribute to the events. At present, it is difficult to detect an EBV-specific component in the action of the T-cells in the acute phase of mononucleosis exerted on B-cells. However, for the clinical course of the disease the activation of T-cells is important. The activated T-cells may control and also eliminate the B-cells infected by EBV. In addition to the immunity which develops during the disease, th immunoregulatory mechanism is likely to have a role in the inhibition of B-cell proliferation.

Antigens, Viral↗

Cell-mediated immune reactions in three patients with malignant lymphoproliferative diseases in remission and abnormally high Epstein-Barr virus antibody titers.

Two patients with Hodgkin's disease in remission and one chronic lymphatic leukemia patient with extraordinarily high anti-Epstein-Barr virus (EBV) (viral capsid antigen) antibody titers (greater than 10,000) were selected to study a spectrum of cell-mediated immune responses, including natural killer, interferon-boosted killer, antibody-dependent lymphocytotoxicity, and T-cell-mediated reactions. The purpose was to compare these reactions in patients with immunosuppression and a high EBV load who can hold their EBV-carrying cells under control with the corresponding reactions in patients with EBV-carrying lymphoproliferative disease. In contrast to the latter group, the three patients of the present study showed a less profound and less general suppression of the immune responses. Multiple effector mechanisms probably safeguard against the proliferation of EBV-transformed B-cells. Clinically manifest EBV-carrying lymphoproliferative disease occurs only in very severe immunodeficiencies effecting multiple effectors.

Adolescent↗